2007

Veterinary

Developmental Anatomy

Veterinary Embryology
Class Notes
(CVM 6100)

by

Thomas F. Fletcher, DVM, PhD

and

Alvin F. Weber, DVM, PhD

1
 CONTENTS

Early Embryogenesis .....................................................3

Musculo-Skeletal Development...................................15

Serous Body Cavities....................................................21

Cardiovascular System ................................................23

Digestive System ...........................................................30

Respiratory System ......................................................36

Urinary System.............................................................39

Genital System ..............................................................42

Face, Nasal Cavity, Mouth, & Pharynx......................47

Nervous System & Special Senses...............................54

Appendix I. Gametogenesis .........................................66

Appendix II. Mitosis and Meiosis ...............................68

Appendix III. List of Anomalies..................................72

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 Early Embryogenesis
Embryogenesis, the formation of body structures & organs (organogenesis), requires cell
division (proliferation) and cell differentiation (specialization) to produce the great variety of cell
types and extracellular products found in the body. Gene expression (and the resultant protein pro-
duction) is the ultimate explanation for the process of cell differentiation and embryogenesis. The
genetic expression of a particular cell depends on its previous genetic history (commitment) and its
current cellular environment (intercellular communication).

Cell Differentiation
stem cell committed cells specialized cell
pyramidal neuron
e.g., neuroblast
ectoderm neural epithelium stellate neuron, etc.
astrocyte
glioblast
oligodendrocyte

Cell differentiation is the result of cells expressing some genes and suppressing others
within a common genome. Cells differ because they produced different proteins/peptides.
Proteins & peptides are:
— structural components (cytoskeleton or extracellular structures)
— enzymes (controlling cell metabolism)
— secretory products (e.g., hormones; digestive enzymes; etc.)
— channels & pumps (passage of molecules across membranes)
— receptors (communication, etc.)

Embryonic Period -defined as the time from fertilization to the earliest (primordial) stages of
organ development (about 30 days in dog, cat, sheep, pig; almost 60 days in horse, cattle, human).

Fetal Period -the time between the embryonic period and parturition (the end of gestation), during
which organs grow and begin to function.

Fertilization:
Refers to the union of a haploid oocyte with a haploid spermatozoon to produce a diploid
zygote (a single cell capable of developing into a new individual)

Oocyte (enveloped by a zona pellucida (glycoprotein membrane) and corona radiata (granulosa cells) at ovulation)
— selective follicles mature at each cycle (in response to circulating FSH hormone from the pituitary)
— primary oocytes resume meiosis following ovulation (having been suspended in Meiosis I since before
birth by inhibitory secretion of follicle granulosa cells)
— secondary oocytes complete meiosis (Meiosis II) following fertilization (if unfertilized they degenerate).

Spermatozoa (several hundred million per ejaculate)

— propelled from vagina to uterine tube by contraction of female genital tract
— undergo capacitation (removal of surface proteins that impede making contact with oocyte)
— undergo acrosomal reaction (enzyme release) after binding to zona pellucida (binding triggers release
of acrosomal enzymes that denature zona pellucida proteins to facilitate penetration
by the reactive sperm).

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 Fertilization details:
Fertilization begins with gamete fusion (zygote formation). The fusion of a spermatozoon with a
secondary oocyte takes place in the uterine tube, near the ovary:
— to begin, a spermatozoon binds to a specific glycoprotein on the zona pellucida that
surrounds the oocyte [this recognition process precludes union with foreign sperm];
— the spermatozoon releases degradative enzymes (acrosomal reaction) that allows the
sperm cell to penetrate the zona pellucida;
— spermatozoon and oocyte plasma membranes fuse (the secondary oocyte completes meiosis);
— the oocyte precludes fusion with other sperm by immediately canceling its
membrane potential (via Ca++ influx) and then by denaturing its zona pellucida
(via enzymes released by exocytosis from oocyte cytoplasmic granules);
— male & female haploid pronuclei make contact, lose their nuclear membranes, and begin
mitosis (mitosis begins 12 hours after sperm fusion; DNA synthesis takes place before mitosis)
Fertilization ends with the initiation of zygote cell division (the start of cleavage)

Cleavage:
This term refers to the series of mitotic divisions by which the large zygote is fractionated into
numerous “normal size” cells. Each daughter cell of the cleavage process is termed a blastomere.
— cleavage begins with a zygote, progresses through compaction to a morula stage and
terminates at the start of the blastocyst (blastula) stage
— the first eight blastomeres are undifferentiated and have identical potential in domestic mam-
mals; thereafter, blastomeres differentiate into inner & outer cells with different missions
Note: The first cleavage division occurs 1 to 5 days following ovulation (depending on species),
thereafter cells divide about once every 12 hours;
As many as eight generations of mitoses may occur without intervening cell growth (cytoplasmic
increase). Thus, e.g., one 150 micron diameter zygote can becomes a collection of 256
cells, each about 7 microns in diameter.

First Second
Cleavage Cleavage Blastula
Division Division Morula (Blastocyst) inner
outer cell
zona blastomeres ma ss
pellucida

blastocoele

blastomeres
inner
blastomeres trophoblasts

A morula [L.= small mulberry] is a solid ball of blastomeres, within a zona pellucida. A
morula typically consists of 16 to 64 blastomeres = four to six cell divisions. Blastomeres become compacted;
cells packed on the inside differentiate from those along the surface of the morula:
— outer blastomeres become flattened and form tight junctions (resulting in reduced permeabil-
ity to fluids); they develop the capacity to secrete fluid (internally); they are destined to
become trophoblasts which form the chorion & amnion (fetal membranes);
— inner blastomeres form gap junctions to maximize intercellular communication; they are des-
tined to become inner cell mass which forms the embryo (plus two fetal membranes).
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 Note: • As few as three inner blastomeres are sufficient to produce an entire embryo (and adult).
• When a morula leaves the uterine tube and enters the uterus (uterine horn) it is at about
the 16-cell stage, around 4 to 7 days after fertilization (depending on species).
• The 32-cell stage morula (5-7 days post ovulation) is ideal for embryo transfer in cattle.

A blastocyst (or blastula) develops during week two following rupture of the zona pellucida.
It consists of a large number of blastomeres arranged to form a hollow (fluid filled) sphere/cylinder
containing an inner cell mass (embryoblast), a collection of cells localized inside one pole (end) of
the blastula. The surface cells of the blastocyst are designated trophoblasts, and the fluid cavity is
called a blastocoele. Eventually the blastocyst attaches to the uterine wall (implantation).
Cleavage in fish, reptiles, and birds:
Large quantities of yolk impede cell division during cleavage. Thus a blastodisc
(rather than a spherical or elliptical blastocyst) is formed at the animal pole of the egg.
A telolecithal ovum (egg with large amounts of asymmetrically distributed yolk) has its nucleus
displaced to one end (pole). Such an ovum has an animal pole where the nucleus is located and an oppo-
site vegetal pole where yolk is concentrated. Cleavage is partial (meroblastic): cells divide more rapidly
(completely) at the animal pole than at the vegetal pole. The result is many, small blastomeres (micromeres)
at the animal pole and few, large macromeres at the vegetal pole. (Cleavage is completed and gastrulation is
underway and the conceptus is composed of about 60,000 cells by the time a chicken egg is laid.)
In contrast, mammalian ova have meager amounts of yolk (oligolecithal ova) which is uniformly
distributed (isolecithal). Cleavage is holoblastic (total): each blastomere division produces two equal-size
daughter cells. Thus animal and vegetal poles are not evident in mammalian ova.

TwiNs
Monozygotic: identical (same genetic composition) twins can result from either:
1] separation of early blastomeres (up to the 8-cell stage)—each separate
blastomere(s) develops into an independent conceptus [conceptus = embryo and
placental membranes]; or
2] separation of inner blastomeres within a single morula—each separate
blastomere(s) develops into an independent embryo and the two embryos share a
common placenta (this is less common than the first possibility).
Note: Diplopagus (Conjoined; Siamese) twins, as well as double heads, etc. types of
anomalies are the result of separations later in embryonic development.
Dizygotic: fraternal twins result when two (or more) zygotes develop “independently”
during the same pregnancy (independence can be compromised by fusion of fetal mem-
branes and blood supplies). It is possible for fraternal blastomeres to merge and produce
a single conceptus that has two different genotypes represented among its population of
cells (a chimera).

NOTE: Germ layers are formed during gastrulation.

Ectoderm, mesoderm and endoderm are designated primary germ layers because origins
of all organs can be traced back to these three layers.
Ectoderm forms epidermis of the skin, epithelium of the oral and nasal cavities, and the
nervous system and sense organs.
Mesoderm forms muscle and connective tissue, including bone, and components of the
circulatory, urinary and genital systems.
Endoderm forms mucosal epithelium and glands of respiratory and digestive systems.

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Gastrulation:
Gastrulation is the morphogenic process that gives rise to three germ layers: ectoderm, meso-
derm, and endoderm. (In a gastrula [Gr.= little stomach] one can see evidence of primitive gut formation.) Gas-
trulation includes the following sequence, beginning with a blastocyst:

— A thickened embryonic disc becomes evident at the blastocyst surface, due to cell prolifera-
tion of the inner cell mass cells. Trophoblast cells overlaying the inner cell mass degenerate in
domestic mammals (in some mammals, e.g., mouse and human, trophoblast cells overlaying the inner cell
mass separate and, instead of degenerating, become amnionic wall.)

— From the inner cell mass, cells proliferate, break loose (delaminate), and migrate to form a
new cell layer inside the trophoblast layer. The new layer of cells is called the hypoblast; it
forms a yolk sac. The remaining inner cell mass may henceforth be called epiblast.

— On the epiblast surface, a primitive streak forms as differential cell growth generates a pair of
ridges separated by a depression. [NOTE: The primitive streak defines the longitudinal axis
of the embryo and indicates the start of germ layer formation.]

— The separation of the hypoblast layer from the epiblast establishes a space (coelom/celom)
deep to the primitive streak. Subsequently, the coelom is temporarily filled by mesoderm that
undergoes cavitation to restablish the coelom that gives rise to body cavities.

— Epiblast cell proliferation along primitive streak ridges becomes the source of a cellular migra-
tion through the streak depression. The migrating cells form endoderm & mesoderm layers.

Hypoblast Formation (three stages)

embryonic
embryonic disc
disc
magnified degenerating
trophoblast

blastocoele
inner
cell mass delaminating
trophoblast hypoblast cells
layer

hypoblast
layer

epiblast epiblast

coelom trophoblast
layer

yolk sac
(primitive gut)
coelom hypoblast
layer

yolk sac
(primitive gut)
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 — Initial migrating cells join the Dorsal View of Embryonic Disc
hypoblast layer, forming embry-
onic endoderm. (The hypoblast notochord
constitutes yolk sac endoderm.)
— The majority of migrating cells
primitive
enter the coelom as primary
node
mesenchyme and become meso-
derm. The primary mesenchyme primitive
migrates laterally and cranially streak
(but not along the midline region
primary
directly cranial to the primitive mesenchyme
streak where notochord will
form). [Mesoderm is divided
into: paraxial, intermediate, and NOTE: Arrows indicate the spread of primary
mesenchyme through the primitive streak
lateral regions.] and between the epiblast and hypoblast

— Cavitation re-establishes a coelom (hoseshoe-shaped) within the lateral mesoderm. The

mesoderm splits into two layers bordering the coelom—somatic mesoderm is attached to the
ectoderm and splanchnic mesoderm is joined to endoderm.

— The remaining epiblast becomes ectoderm which forms skin epidermis & nervous system.

primitive streak
epiblast (ectoderm)

hypoblast endoderm primary mesenchyme (mesoderm)

Formation of the notochord:

The notochord is a rod-shaped aggregate of cells located cranial to the primitive streak of
the embryo. It occupies the midline coelomic space between ectoderm and endoderm that was not
invaded by migrating primary mesenchyme.
The notochord is important because it induces formation of the head, nervous system devel-
opment, and somite formation. It marks the future location of the vertebral column and the base of
the cranium. Its ultimate fate is to become the nucleus pulposus of intervertebral discs.
The notochord develops from the primitive node located at the cranial end of the primitive streak. From the
node, mesoderm-forming cells proliferate and migrate forward into the future head region where they become the rod-
shaped notochord.
Longitudinal Section Through Primitive Node and Notochord

primitive streak notochord cells head process

ectoderm
primitive node

endoderm mesoderm cells

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Early Formation of the Nervous system (Neurulation):
Neurulation refers to notochord-induced transformation of ectoderm into nervous tissue. The
process begins during the third week in the region of the future brain and then progresses caudally
into the region of the future spinal cord.

The following steps are involved in Neurulation

neurulation: paraxial mesoderm
— ectodermal cells overlaying neuroectoderm intermediate mesoderm
the notochord become tall
columnar (neuroectoderm); lateral mesoderm
they form a thickened area somatic
designated the neural plate. notochord splanchnic
Other ectodermal epithelium is endoderm
flattened.) neural groove coelom
ectoderm
— a neural groove is formed.
Edges of the neural plate be-
come raised on each side of somite
a midline depression. (Apical
ends of individual neuroectoder-
mal cells constrict.)

— a neural tube is formed as neural tube neural crest

the neural groove is closed
by midline merger of its
dorsal edges. The tube
separates from non-neural
ectoderm which unites dor-
sal to it. (Tube formation begins
in the cranial cervical region of
the central nervous system and
progresses cranially and caudally until anterior and posterior neuropores, the last openings, finally close.)

— bilaterally, where the neural groove is joined to non-neural ectoderm, cells detach as the
neural groove closes; the cells proliferate and assume a position dorsolateral to the neural
tube—forming neural crest.

NOTE:
Neural tube becomes the central nervous system, i.e., the brain and spinal cord.

Neural crest cells are remarkable for the range of structures they form. Some cells mi-
grate dorsally and become pigment cells in skin. Others migrate ventrally and become
neurons and glial cells of the peripheral nervous system, or adrenal medulla cells. In
the head, neural crest forms mesenchyme (ectomesenchyme) which becomes meninges,
bone, fascia, and teeth.

Note: Each organ system has a critical period during development when it is most sensi-
tive to external agents (teratogens) that produce birth defects.
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somite formation:
somites are blocks of mesoderm
located just lateral to the notochord. Gener- otic placode
ally, there are a pair of somites for every
vertebra and a half dozen somite pairs in the
head. The number of somites in an embryo
is indicative of age because somites develop
chronologically, in craniocaudal order. optic
placode
Note: The ventromedial portion of a somite
develops into a sclerotome (which orms
f
branchial
vertebrae, ribs, & basal bones of the
arches
skull), the lateral portion becomes a
dermatome (skin dermis), and the rest
of the somite forms a myotome (skeletal heart
muscle).
umbilical
Somites develop as follows: stalk
— mesoderm accumulates on each
side of the notochord; this medially
positioned mesoderm is designated
paraxial mesoderm
— progressing from rostral to caudal
somites
over time, transverse fissures divide
the paraxial mesoderm into blocks
— each block is a somite (cells within a
block re-orient 90°, from transverse to the
notochord to longitudinal to the notoc hord)
— head (occipital) somites develop
from proliferation of local mesenchyme lateral to the cranial end of the notochord
— rostral to the notochord, mesenchyme forms quasi-somites, called somitomeres; they migrate
into branchial arches and form muscles of the jaw, face, pharynx, and larynx.
NOTE:
Mesoderm can exist in two morphologic forms: mesenchyme and epithelium:
Mesenchyme features aggregates of stellate cells within an abundant extracel-
lular matrix composed of fluid and macromolecules (polymers).
Epithelium refers to organized cells having distinct apical and basal surfaces,
the latter commonly rests on a basal lamina produced by epithelial secretion.
Mesoderm can transform from a mesenchyme to an epithelium and vice versa: The
mesoderm that streams through the primitive streak is primary mesenchyme.
Somatic, splanchnic, and somite mesoderm can be temporarily an epithelium.
The temporary epithelium transforms to a secondary mesenchyme which ulti-
mately forms muscle and connective tissue (including cartilage, bone, liga-
ments, tendons, dermis, fascia, and adipose tissue).
Thus, the term “mesenchyme” refers to the morphologic appearance of embryonic tis-
sue. Although most mesenchyme is mesoderm, the other germ layers can also
form mesenchyme during organ development.

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Development of a Cylindrical Body:
The early embryo is flat, but the vertebrate body plan features a cylindrical theme—various
cylindrical structures (derivatives of the gut, neural tube, notochord, etc.) enclosed within a cylindri-
cal body. Transition from a flat embryo to a cylindrical one involves the following developments:

Head Process: Three Stages of

• The cranial end of the embryo grows dor- Head Process Formation
sal and forward so that it projects above an area (longitudinal views)
originally in front of the embryo.
• The cylindrical head process elongates by
growth from its base in front of the primitive ectoderm
node. Consequently, the most anterior part of the embryo mesoderm
is the oldest. The elongation incorporates the most anterior en doderm
half-dozen somites into the future head. yolk sac
• Within the head process, endoderm is
reflected ventrally upon itself, forming a blind-
ended foregut (future pharynx). head
process
Tail Fold:
• At the caudal end of the embryo, a cylindri-
cal tail fold is formed in a manner similar to that
of the head process.
• Folded endoderm encloses a blind hindgut . oral plate

Lateral Body Folds:

• As the head process elongates upward &
forward, a subcephalic pocket (space) is formed head
ventral to the head process, between the head process
process and extra-embryonic tissue. The bi-
lateral margins of the pocket are lateral body subcephalic
folds—which constitute the continuity between pocket
the elevated embryo and the relatively flat extra- pharynx
embryonic tissue.
Dorsal
View elevated • Similar folds
head
exist caudally in as-
process
sociation with the tail
lateral process.
yolk sac
body pericardium
fold • As the embryo
grows and is elevated dorsally, lateral body folds adduct and join ven-
trally, establishing a tubular embryo separated from flattened extra-em-
bryonic tissue.
primitive • Progressing caudally from the head process and cranially from the
node
tail fold, ventral fusion of lateral body folds stops at the umbilicus—leav-
primitive ing a ventral opening in the body wall that allows vessels and the yolk
streak sac and allantois to enter the embryo (and communicate with the gut).

10
 • Ventral fusion of lateral body folds Mesoderm
distinguishes the embryo from extra-embry- = somite neural tube
onic tissue (fetal membranes): = intermediate notochord
= lateral fore gut
Embryonic coelom (future body cavities
of the trunk) is distinguished from extra- Lateral
embryonic coelom within fetal membranes. Body
Somatopleure (somatic mesoderm + Folds
ectoderm) that forms body wall is distin- embryonic
coelom
guished from that forming fetal membranes mesentery
(chorion and amnion).
Splanchnopleure (splanchnic mesoderm
+ endoderm) merges bilaterally to form gut
somatopleure extra-emb ryonic
and mesentery, differentiated from extra- coelom
splanchnopleure yolk
embryonic yolk sac (and allantois). sac

Pharyngeal (Branchial) Arches:

In the head region, anterior to the embryonic coelom, mesenchyme between ectoderm and
endoderm forms a series of dorso-ventral arches demarcated by grooves. Only three pharyngeal
arches are externally evident in mammals. Each arch contains a vessel (aortic arch). Within each arch, mesoder-
mal mesenchyme which gives rise to muscle is augmented by ectomesenchyme (migrated from neural crest) which gives
rise to bone and fascia.
The first pharyngeal arch develops into upper and lower jaws and muscles of mastication.
The second into hyoid bones and muscles of the face. The remaining pharyngeal arches form hyoid
bones, larynx and associated muscles. Each arch is innervated by a particular cranial nerve.
The pharynx (foregut) develops five bilateral diverticula that internally demarcate the
pharyn- geal arches. These pharyngeal pouches develop into auditory tube, parathyroid glands,
thymus, etc.
NOTE: In fish, five or six branchial [Gr. = gill] arches are well developed. Cells degenerate where
branchial grooves and pharyngeal pouches meet so that the pharynx communicates with the
outside (this occurs only temporarily between the first two arches in mammals). The first arch
forms the jaw apparatus and the rest form gill arches separated by gill slits.

Flexures:
The tube-shaped embryo undergoes three flexures that make it C-shaped. The first occurs
in the future midbrain region, the second in the future neck region, and the third occurs in the tail
region.

Cardiovascular system:
• The cardiovascular system develops early (in the third week after the start of the nervous
system), as the embryo enlarges and diffusion alone becomes inadequate for tissue preservation.
• Angiogenesis (formation of blood vessels) begins in splanchnic mesoderm of the yolk sac,
in the form of blood islands composed of mesenchyme and hemocytoblasts. The latter forms blood
cells and the mesenchyme forms vesicles lined by endothelium. The vesicles coalesce to form vascu-
lar channels and then blood vessels (the latter are formed by budding, fusion, & enlargement).
• Vessels are formed first in extra-embryonic tissue: vitelline (yolk sac) and umbilical (allan-
toic) vessels appear first.
• Ventral to the pharynx, bilateral vessels merge to form a tubular heart; dorsal and ventral aortae are connected
by aortic arches. Also, cranial and caudal cardinal veins return embryonic blood to the heart and umbilical veins return
placental blood to the heart. None of these vessels will persist as such in the adult.
11
Placentation:
The placenta is the area(s) of apposition between uterine lining and fetal membranes where
metabolites are exchanged for sustaining pregnancy.
Apposition areas (placental types) may be diffuse (pig), zonary (carnivore), discoid (primates
& rodents), or involve placentomes. A placentome is a discrete area of interdigitation between a ma-
ternal caruncle and a fetal cotyledon. Equine placentas are microcotyledonary (microplacentomes
are distributed diffusely). Ruminant placentas consist of rows of relatively large placentomes.
Placentas (placentae) may also be classified according to the tissue layers separating fetal and maternal blood.
Uterine epithelium, uterine connective tissue and uterine endothelium may be eroded, giving rise to four placental types:
epitheliochorial (swine, equine, cattle); synepitheliochorial, formerly called syndesmochorial, (sheep, goats); endothelial
chorial (carnivore); and hemochorial (primates & rodents).

chorion
allantois
embryo amnion

somatopleure coelom
gut

splanchnopleure yolk sac

Fetal membranes:
Four fetal membranes develop in a conceptus. Two arise from the trophoblast layer of the
blastocyst and are continuous with the somatopleure of the embryo. Two arise from the inner cell
mass of the blastocyst and are continuous with splanchnopleure of the embryo; these two membranes
are vascular. The four fetal membranes are:
1. Chorion — from trophoblast, forms the outer boundary of the entire conceptus.
2. Amnion — from trophoblast, is formed by folds of chorion is domestic animals (in humans,
amnion forms by caviation deep to a persistent trophoblast). The amnion encloses the embryo within a fluid-
filled amnionic cavity.
3. Allantois — from the inner cell mass, develops as an outgrowth of hindgut splanchno-
pleure. The allantois grows to fill the entire extra-embryonic coelom, with fluid-filled allantoic
cavity. The outer surface of allantois binds to the inner surface of chorion and the outer surface of
amnion. The allantois is highly vascular and provides the functional vessels of the placenta, via um-
bilical vessels.
4. Yolk sac — from the inner cell mass, develops early (with hypoblast formation) and is
continuous with midgut splanchnopleure. Supplied by vitelline vessels, yolk sac is most important in
egg laying vertebrates. It forms an early temporary placenta in the horse and dog.

Note: The term conceptus refers to the embryo or fetus plus its fluid-filled fetal membranes.

implantation
Following zona pellucida rupture, the blastocyst is innitially free in the uterine lu-
men (nourished by uterine glands). Implantation of the mobile blastocyct is a gradual
process beginning with apposition leading to adhesion (or invasion in the case of the
human & Guinea Pig). Approximate implantation times are: one week (human); two weeks (dog,
cat, sheep), 3-5 weeks (cattle), 3-8 weeks horse; or delayed up to 4 mons (deer, bears).
12
 amnionic cavity
chorion
(somatopleure)
hindgut

amnion extra-embryonic coelom

(somatopleure) (lined by mesoderm)
heart
allantois
embryonic (splanchnopleure)
vitelline membrane
coelom
(splanchnopleure)
yolk
sac
allantoic
anllantoic
cavity
cavity

somites

posterior
neuropore

umbilical
head stalk
process heart tail
process
branchial
arch

caudal
cranial otic placode notochord dorsal aorta cardinal vein
cardinal
vein somites

stomach

hindgut
umbilical
heart
aortic arch stalk
optic cup ventral aorta
pharyngeal umbilical
allantois
pouch vein
yolk sac
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 Fetal Components of Placentae

Porcine Chorionic Surface

(folds; diffuse placental contact)
(chorion without allantois)
necrotic tip

cervical star
(region over cervix)

Equine Chorionic Surface

(microcotyledons)
Bovine Chorionic Surface
(rows of cotyledons)

Carnivore Chorionic Surface

(zonary placental contact)

Human/Rodent Chorionic Surface

(discoid placental contact)
marginal
hematoma
marginal
hematoma

14
 Musculo-Skeletal System
(Trunk, Limbs, and Head)
ectoderm
somite:
General Statements: dermatome
myotome
Bilaterally, paraxial mesoderm become sclerotome
somites and somitomeres. (Somitomeres develop ros- neural crest intermediate
tral to the notochord in the head. They are like somites, but mesoderm
neural tube
smaller and less distinctly organized.)The mesoderm somatic
comprising each somite differentiates into three mesoderm
notochord
regions: endoderm
aorta
- dermatome (lateral) which migrates to
coelom
form dermis of the skin
- sclerotome (medial) forms most of the splanchnic mesoderm
axial skeleton (vertebrae, ribs, and base of the skull). Mesoderm Regions
-myotome (middle) forms skeletal mus-
culature. Individual adult muscles are produced by merger of adjacent myotomes.

Note: Nerves make early connections with adjacent myotomes and dermatomes, establishing
a segmental innervation pattern. As myotome/dermatome cells migrate to assume adult positions,
the segmental nerve supply must follow along to maintain its connection to the innervation target.
(Recurrent laryngeal & phrenic nerves travel long distances because their targets migrated far away.)

Skin. Consists of dermis and epidermis.

Epidermis, including hair follicles & glands, is derived from ectoderm. Neural crest cells
migrate into epidermis and become melanocytes. (Other neural crest cells become tactile disc receptors.)
Dermis arises from mesoderm (dermatomes of somites). Each dermatome forms a continu-
ous area of skin innervated by one spinal nerve. Because adjacent dermatomes overlap, a locus of
adult skin is formed by 2 or 3 dermatomes, and innervated by 2 or 3 spinal nerves.

Muscle. Muscles develop from mesoderm, except for

muscles of the iris which arise from optic cup ectoderm. Cardiac and
somitomeres somites
smooth muscles originate from splanchnic mesoderm.
in pharyngeal
All skeletal muscle is derived from paraxial meso- arches
derm that forms somites and, in the rostral region of the
head, somitomeres.
Mesodermal cells of the myotome region of each heart limb
eye bud
somite/somitomere differentiate into myoblasts which fuse head
to form multinucleate muscle cells that synthesize myosin
& actin and appear striated. Somites & Somitomeres
Muscle development requires innervation. Also,
muscles and tendons must be under tension (stretched by growing bone) in order to grow to proper
lengths.

Note: Each anatomical muscle is genetically allocated a specific number of myoblasts that is deter-
mined by the time of birth. Thereafter, muscle cell growth is due solely to cellular hypertro-
phy. Regeneration (hyperplasia) of adult muscle cells does not occur.

15
 Bone. Bones originate from paraxial mesoderm (endochondral axial skeleton from sclero-
tomes), somatic mesoderm (endochondral appendicular skeleton), or ectomesenchyme (intramem-
branous bones of the calvaria and face from neural crest). Ligaments, tendons, and muscle-related connective
tissue originate from local mesenchyme or ectomesenchyme.
Thus, most bones are formed endochondrally (ossification of a cartilage model), but bones
of the calvaria (top of the skull) and the face are formed intramembranously (ectomesenchyme cells
become osteoblasts directly rather than becoming chondroblasts).

Endochondral bone formation:

-local mesenchyme undergoes condensation; some cells differentiate into chondroblasts
-chondroblasts secrete matrix to produce a cartilage model of the future bone; the model is
surrounded by perichondral fibrous tissue
— the diaphysis of the cartilage model undergoes ossification first; epiphyseal ossification
occurs later; physis ossification is postponed until bones stop growing in length.
-overall bone shape is genetically determined; surface irregularities of bone are acquired
due to localized tension (stress) produced by ligaments and tendons.

Joints. Condensation of mesenchyme produces an interzone region within perichondral tis-

sue connecting adjacent cartilage models of bones. According to the nature of the future joint, the
interzone becomes fibrous connective tissue, or fibrocartilage, or a synovial cavity.

Synovial joints form as follows: cavitation

perichondral
-mesenchyme at the center of the synovial
layer cavity
interzone undergoes cavitation and t he
tissue bordering the cavity become syno- interzone ligament
vial membrane; uneven expansion of the cartilage synovial
(bone) membrane fibrous
synovial cavity creates synovial folds (the capsule
interzone mesenchyme also forms intra-articular
Synovial Joint Development
ligaments and tendons where these are present);
-perichondral tissue surrounding the interzone becomes joint capsule and localized thick-
enings of the joint capsule forms ligaments.

Note: Muscle activity is essential for proper synovial joint development after the
joint cavity develops. Joints must move during in utero and postnatal develop
ment to prevent ankylosis (fixed/frozen joint).

Regional Specifics

Trunk Region:
Skeletal musculature is formed by somite myotomes which fuse to form broad muscles that
are segmentally innervated (each myotome brings its own innervation as it merges with adjacent
myotomes). Myotome accumulations segregate into a dorsal mass (epimere) innervated by dorsal
branches of spinal nerves and a ventral mass (hypomere) innervated by ventral branches of spinal
nerves. The epimere becomes epaxial muscles and the hypomere becomes hypaxial muscles.
Sclerotomes give rise to vertebrae and ribs. The sternum develops differently, from chondrification/os-
sification of somatic mesenchyme of the ventral thorax.

16
 epaxial
Formation of Vertebrae and Ribs: muscles
- sclerotome regions of somites migrate & become a con- dorsal
tinuous mass surrounding the notochord and neural tube. Thus the branch
original somite segmentation is lost
-the continuous mass differentiates into diffuse & dense ventral
branch
regions per original sclerotome. The diffuse region from one
hypaxial
somite combines with the dense region of an adjacent somite to muscles
produce a cartilage model of one vertebra.
-between newly formed vertebrae (intervertebral disc
regions) sclerotome mesenchyme forms annulus fibrous and
notochord forms nucleus pulposus (notochord degenerates in the
region of the vertebral body)
spinal
-ribs develop as processes of thoracic vertebrae. nerve
gut
Note: As a result of the above re-segmentation, vertebrae are
shifted relative to other segmental structures (see next
coelom
page). Consequently, muscles span adjacent vertebrae;
spinal nerves traverse intervertebral foramina (located Myotome
Segregation
dorsal to intervertebral discs); and embryonic intersegmental
arteries become spinal arteries that run along side vertebral bodies.

Vertebral anomalies include: stenosis of the vertebral canal; mal-articu-

lation; hemivertebra; and spinal bifida (absent vertebral arch). The notochord,
neural tube, and neural crest all play a role directing somite differentiation and
vertebral segmentation (formation).

Note: The dens originates as the body of vertebra C1 (atlas), but it

fuses with vertebra C2 (axis). L-2

Limbs:

Limbs grow outward from body wall somatopleure as limb

buds. Bone, cartilage, and connective tissue of the limb arise from
somatic mesoderm of the limb bud. Dermis and skeletal muscle
come from dermatome and myotome migrations into the limb.
L-3
Limb Morphogenesis:
— a limb begins as a limb field (an area of somatopleure
committed to forming a limb)
-next, a limb bud is produced by localized proliferati on &
condensation of mesenchyme, covered by ectoderm
-regions of the limb develop in proximodistal order as the
limb bud elongates (the shoulder/hip appears first, the manus/pes is
the last to be added)
— the distal end of the limb bud (footplate) is flattened ike
a paddle and ectoderm along its outer margin thickens to form n
apical ridge (the ridge is induced to form by underlying mesoderm and it
induces the mesoderm to continue growing and differentiating into a limb)
Canine Dermatomes
17
 Sclerotomes to Vertebrae

neural tube
dorsal root
neural tube segments ectoderm

spinal n. somite

sclerotome
notochord
myotome

caudal cranial
dermatome

continuous mass

sclerotome myotome

dense dif
diffuse spinous process
ossification transverse process

vertebral rib
canal tubercle

rib
head
vertebral
body notochord

vertebra
muscle
intervertebral disc

18
 -mechanically, limb growth consists of:
- elongation of a dorsoventrally flattened limb bud
- ventroflexion of the distal half of the limb (ventral now faces medially)
- pronation of the distal half (previous medial surface now becomes caudal) foot plate
-separate digits are produced by interdigital necrotic zones (species
with fewer digits undergo further degeneration and/or fusion of digits);
-local mesenchyme condenses to form cartilage models of limb bones
-myotome cells migrate into the base of the limb forming extensor &
flexor muscle masses that subsequently segregate into individual muscles;
-vessels and nerves grow into the limb.
Clinical considerations: cell death
Achondroplasia (dwarfism; Dachshund) — inherited, systemic prema-
ture ossification of physes of extremities.
Arthrogryposis [Gr. gryposis = crooked] can result from malformed joints,
denervation, abnormal muscle tension, or impaired mobility in utero. digit
Polydactyly (extra digits); syndactyly (fused digits); brachydactyly
(stumpy digits Gr. dactylos = digit]
Amelia (no limb); meromelia (absence of part of limb); micromelia Manus/Pes
(small limb Gr. melos = limb] Development
Note: phocomelia (seal limb) = absence of proximal segment(s) of limb
was a consequence of pregnant women taking thalidomide in 1950s.

Head Region:
The head consists of a cranium, which contains the brain within a cranial cavity, and a face.
The face develops separately from the frontonasal process and first pharyngeal arch. Since the face
and cranium have different embryonic origins they can be independently influenced genetically (e.g.,
in the case of brachycephalic breeds) or by teratogens.

Skull. Bones of the base of the cranium develop endochondrally; the relatively flat bones that
comprise the calvaria (roof of the cranium) and the face develop intramembranously. (The mandible has
a complex origin involving both endochondral and intramembranous development.)
The endochondral bones are formed from sclerotomes of somitomers and sclerotomes of the
first four somites (occipital somites).
The intramembranous bones arise from ectomesenchyme (mesenchyme derived from neural
crest), which gives rise to cartilage, bone, and connective tissue of the face and dorsal head. Intramem-
branous bones articulate by means of fibrous joints called sutures. Widened suture areas, at the corners of growing bones,
are called fontanels. utures and fontanels allow bony plates to overlap one another during parturition.

Regions of the Skull

calvaria of cranium
(intramembranous )
face
(intramembranous)

base of cranium (endochondral ) 19

 Note: Auditory ossicles arise endochondrally from branchial arches I (malleus & incus) and II (stapes).

Muscles. Muscles of the head arise from somitomeres (seven) and somites (four occipital so-
mites).
Somitomere myotomes migrate to the orbit (two giving rise eye muscles) or they migrate to
pharyngeal arches (becoming muscles of mastication and facial expression muscles).
Somite myotomes become tongue and neck muscles and they migrate to pharyngeal arches
(IV-VI), becoming pharyngeal, laryngeal & esophageal muscles.
Cranial nerves establish early connections with adjacent somitomeres & somites and ac-
company them to definitive muscle sites. Pharyngeal arches are each innervated by specific cranial
nerves (I=trigeminal; II=facial; III=glossopharyngeal; IV-VI=vagus).

Pharyngeal (Branchial) Arch Summary:

Ectomesenchyme migrates to pharyngeal arches to form connective tissue, cartilage and
bone. Somitomere/somite myotomes migrate into the arches and give rise to skeletal muscle. Each
arch is innervated by a particular cranial nerve.
First arch. (innervated by cranial nerve V)
-jaw bones (mandible & maxilla); also, ossicles of the middle ear (incus & stapes)
-muscles of mastication, plus rostral digastricus, mylohyoid, & tensor tympani mm.

Second arch: (innervated by cranial nerve VII)

-hyoid bones & stapes (ossicle of the middle ear)
-muscles of facial expression, including caudal digastricus & stapedius mm.

Third arch: (innervated by cranial nerve IX)

-hyoid bones
-one pharyngeal muscle (stylopharyngeus mm.)

Arches IV through VI: (innervated by cranial nerve X)

-laryngeal cartilages
-pharyngeal mm & cricothyroid m -innervated by cranial branch of X
-intrinsic laryngeal mm -innervated by recurrent laryngeal n. of X

20
 Formation of Body (Serous) Cavities
Serous cavities are trunk body cavities lined by serous membrane (mesothelium). In the
adult, serous cavities are: the pericardial cavity, two pleural cavities, and the peritoneal cavity (in-
cluding vaginal cavity extensions of the peritoneal cavity).
Acquiring a three-dimensional understanding of how embryo ectoderm
serous cavities are formed is a challenging exercise. Serous
cavity formation may be summarized as follows: endoderm
• all of the serous cavities develop from a common extrembryonic
embryonic coelom and thus the cavities are continuous until coelom
partitions develop to separate them;
• the individual serous cavities are formed by inward embryonic
growth of tissue folds from the body wall (partitions) and by coelom
outgrowth of coelomic cavity into the body wall (excavation). pericardium

Coelom Development: foregut hindgut

Recall, during gastrulation, that the space between the
coelom
trophoblast and hypoblast is filled by inflow of primary mesen-
chyme that becomes mesoderm. Cavitation within lateral meso-
derm establishes a definitive coelom, bounded by somatopleure yolk
and splanchnopleure. The coelom is horseshoe shaped because sac
cavitation occurs anterior to the embryo as well as bilaterally.
As head and tail processes develop and lateral body Coelom
(Longitudinal View)
folds merge medially (except at the umbilicus), embryonic and
extra-embryonic compartments of the coelom can be differen-
tiated. The former becomes the serous cavities Mesoderm
of the trunk, the latter is within the chorion and = somite neural tube
= intermediate notochord
filled by the allantoic fetal membrane. = lateral fore gut
Formation of the head process brings the
heart and pericardial coelom within the embryo, Lateral
positioned ventral to the foregut. Right and left Body
sides of the embryonic coelom are separated by Folds
embryonic
gut and by dorsal and ventral mesenteries, the coelom
latter fails to develop at the level of the midgut. mesentery
Thus, the embryonic coelom features an
anterior-ventral pericardial compartment, a cau-
dal peritoneal compartment, and bilateral pleural somatopleure extra-emb ryonic
compartments (channels) connecting the peri- splanchnopleure yolk coelom
cardial and peritoneal compartments. Mesoderm sac
lining the coelom forms mesothelium.

Separation of Peritoneal and Pleural Cavities:

In the adult, peritoneal and pleural cavities are separated by the diaphragm. The diaphragm is
formed by a septum transversum, paired pleuroperitoneal folds, and somatic mesoderm. Diaphrag-
matic musculature is derived from somites in the cervical region (C5, 6, 7), where the diaphragm is
initially formed.
21
Details of diaphragm formation include: Diaphragm Formation
— the septum transversum originates as mesoderm in front of the (Caudal View)
heart. As the heart shifts ventral to the foregut, the septum becomes
degenerating
incorporated into the ventral body wall and ventral mesentery caudal to the
mesonephros pleur o-
heart. The septum grows dorsally and forms a transverse partition ventral
to the level of the gut peritoneal
fold
— dorsal to the gut, bilateral pleuroperitoneal folds grow medially
and meet at the dorsal mesentery
— subsequent growth of the pleural cavity into somatic mesoderm
(mesenchyme) will result in body wall mesoderm forming the marginal
regions of the diaphragm (diaphragm musculature). septum
transversum pleu ro-
peritoneal
Separation of Pericardial and Pleural Cavities: canal
In the adult, pericardial and pleural cavities are sepa-
rated by fibrous pericardium. crus of
diaphragm vertebra
Originally in the embryo, the pericardial coelomic cav-
ity communicated with two dorsally positioned pleural cavi-
ties (canals). Subsequently, the cavities become partitioned by aorta
paired pleuropericardial folds and then somatic mesoderm.
esophagus
Details of the separation include:
— bilateral pleuropericardial folds (membranes), which accom-
pany common cardinal veins as they join the heart, converge medially to
unite with the mediastinum (ventral mesentery) and partition the ventral central caudal
vena
pericardial cavity from the dorsal pleural canals; tendon cava
— subsequent ventrolateral growth of the pleural cavities into the
body wall incorporates somatic mesoderm (mesenchyme) into the future
fibrous pericardium.
NOTE: Mediastinum is formed initially by dorsal and ventral diaphragm
muscle
mesenteries of the esophagus.

Growth of Pleural Cavities:

Initially the pleural cavities are small canals into which the lung buds project. As the lungs
grow, the pleural cavities enlarge and appear to carve into the body wall (into somatic mesoderm/
mesenchyme). As a result, somatic mesoderm forms partitions (fibrous pericardium and diaphragm)
that wall off the pleural cavities.

dorsal aorta neural tube

esophagus limb vertebra
lung bud aorta
mediastinum

pleural pleuro- lung

coelom pericardial pleural cavity
fold
heart pericardial body wall
coelom fibrous
preicardial sac pericardium
Early Pleural Cavity Formation Late

22
 Cardiovascular System
Note: The cardiovascular system develops early (week 3), enabling the embryo to grow beyond the short
distances over which diffusion is efficient for transferring O2, CO2, and cellular nutrients &wastes.

Heart:
From a simple tube, the heart undergoes differential growth into a four chambered structure
while it is pumping blood throughout the embryo and into extra-embryonic membranes. Major vessels
form and the heart initiates a peristaltic pumping action during the third week in the dog.

Formation of a Tubular Heart:

amnionic cavity
The first evidence of heart de-
velopment is horse-shoe shaped vessel ectoderm
embryo
formation within the cardiogenic plate,
which is splanchnic mesoderm situated
anterior and lateral to the embryo. As cardiogenic yolk sac endoderm
the head process grows upward and plate mesoderm
outward, the cardiogenic plate shifts
ventral to the pharynx and bilateral embryo
endocardial tubes meet at the midline
& fuse into a single endocardial tube.
Splanchnic mesoderm surrounding the heart
tube forms cardiac muscle cells. yolk sac

Primitive Heart Regions:

Differential growth of the endocardial tube establishes five primitive heart regions:
1] Truncus arteriosus — the output region of
the heart. It will develop into the ascending
aorta and pulmonary trunk. truncus
arteriosus
2] Bulbus cordis — a bulb-shaped region bulbus
destined to become part of the right ventricle cordus
(conus arteriosus).
3] Ventricle — an enlargement destined to
become the left ventricle. ventricle

4] Atrium — a region that will expand to sinus

venosus
become both right and left auricles. L R L
atrium
5] Sinus venosus — a paired region into
R
which veins drain. The left sinus venosus Midline Fusion
Tubular Heart
becomes the coronary sinus; the right is
incorporated into the wall of the right atrium.

Forming a Four-Chambered Heart:

A] The endocardial tube lengthens and loops on itself—this puts the bulbus cordis (right ventricle)
beside the ventricle (left ventricle) and the atrium dorsal to the ventricle.

23
 cranial
B] Venous return is shifted truncus
to the right side. The right sinus ve- bulbus
arteriosus
nosus becomes enlarged and incor- cordis atrium sinus
porated into the future right atrium. venosus
The smaller, left sinus venosus
bulbus
merges into the future right atrium cordis common
as the coronary sinus. ventricle atrioventricular
opening
The atrium expands and overlies ventricle
the interventricular opening, creating a sinus atrium
common atrioventricular opening (canal). venosus
A constriction, the future coronary groove,
separates atria and future ventricles at the Sagittal Section
level of the atrioventricular opening. caudal
Endocardial Tube
C] The common atrio-ventricular opening is partitioned into right and left A-V openings by
growth of endocardial “cushions”. Subsequently, ventral growth of the cushions produces a septum
that closes the interventricular foramen (the original opening between the bulbus cordis & ventricle).
(Incomplete closure of the
interventricular septum (ventricular endocardial
septal defect) results in blood flow truncus cushion
from the left to the right ventricle arteriosus
atrium
and an associated murmur. Large
atrium
defects produce clinical signs of
cardiac insufficiency.)
bulbus interventricular:
cordis foramen
D] The right and left ventricle right septum
ventricles are formed by ven- ventricle left
tral growth and excavation of ventricle
the bulbus cordis and ventri-
cle, respectively. An interven- Ventricle
tricular septum, atrioventricu- Development
lar valves, chordae tendineae,
papillary muscles, and irregularities of the internal ventricular wall are all sculptured by selective
excavation of ventricular wall tissue.

E] Right and left atria are established by formation of an interatrial septum. Septum forma-
tion is complicated by the need, until birth, for a patent (open) septum that allows blood to flow from
the right atrium to the left. The septal opening
is called the foramen ovale. secondary septum
Two septae and three foramina are involved in
dividing the atria: sinuatrial
opening secondary
Interatrial Septum 1 grows from the dorsal foramen
wall of the atrium toward the endocardial cushions at
the atrioventricular canal. The pre-existing Foramen 1 path of
blood flow
is obliterated as Septum 1 meets the endocardial cush-
ions.
Foramen 2 develops by fenestration of the right primary septum
dorsocranial region of Septum 1. atrium (valve of f.ovale)
foramen
Interatrial Septum 2 grows from the cranial ovale
wall of the right atrium toward the caudal wall. The
septum remains incomplete and its free edge forms the
boundary of an opening called the ForamenOvale.
Blood Flow Through Foramen Ovale
24
 NOTE: As long as blood pressure in the right atrium exceeds that of the left atri-
um, blood enters the Foramen Ovale, flows between the two septae and exits
through Foramen-2. When, at birth, pressure is equal in the two atria, Septum-
1 is forced against the Foramen Ovale, acting as a valve to close the foramen
and preclude direct blood flow between the atria.
An atrial septal defect is not a serious developmental anomaly as long as pressure is ap-
proximately equal in the two atria, which is normally the case.

aorta
F] Aorta and pulmonary trunk are formed by
partition of the truncus arteriosus (and adjacent bulbus cor-
caudal
dis). In a spiral pattern, ridges appear along the lumen vena cava pulmonary
wall, grow inward and merge creating a spiral sep- trunk
tum. As a result, the aorta and pulmonary trunk spiral left
around one another. right atrium
atrium
Failure of the septum to spiral leaves the aorta connected
to the right ventricle and the pulmonary trunk to the left ven- left
right ventricle
tricle—a fatal flaw. ventricle

Aortic and pulmonary semilunar valves are

formed like atrioventricular valves, by selective ero-
sion of cardiac/vessel wall. Improper valve sculpturing will
produce valvular insufficiency in the case of excessive erosion or Spiral Arrangement of the
vessel stenosis (narrow lumen) in cases of not enough erosion Aorta & Pulmonary Trunk

aorta or pulmonary trunk vessel wall excavation semilunar Note:

cusp
Neural crest cells mi-
grate to the region of the
truncus arteriosus and
direct its partitioning by
the spiral septum. Abla-
flow
from tion of the neural crest
heart results in anomalies of
the great vessels.
Development of semilunar valves by excavation

Tetralogy of Fallot:
This is a cardiac anomaly that occurs in number of species, including humans. It involves a combination of four
defects all related to a defective spiral septum formation in the truncus arteriosus & bulbus cordis:
• ventricular septal defect;
• stenosis of the pulmonary trunk;
• enlarged aorta that overrides the right ventricle (dextroposition of the aorta); and
• hypertrophy of the right ventricle, secondary to communication with the high pressure left ventricle.

Note: Vasculogenesis begins with blood islands formation in splanchnic mesoderm of the yolk sac
and allantois. Angiogenesis (vessel formation) occurs when island vesicles coalesce, sprout
buds, and fuse to form vascular channels. Subsequently, hematopoiesis (blood cell formation)
occurs in the liver and spleen and later in the bone marrow. The transition from fetal to adult
circulation involves new vessel formation, vessel merger, and degeneration of early vessels.

25
 right
intersegmental aa.

dorsal
aorta caudal
cranial cardinal v. iliac
vitelline a.
cardinal v. branch
umbilical a.
common
cardinal v.

umbilical v.
HEART

aortic ventral
vitelline v.
arch aorta

Early allantoic
Arteries yolk sac
vessels
& Veins vessels

Arteries:

Dorsal and Ventral Aortae:

The embryo develops paired ventral and dorsal aortae. The two ventral aortae receive blood
from the truncus arteriosus. Bilaterally, ventral and dorsal aortae are connected by a series of up to
six aortic arches. Each aortic arch is situated within a pharyngeal (branchial) arch.
Paired ventral aortae fuse to form the brachiocephalic trunk. Caudal to the aortic arches, the
paired dorsal aortae merge to form a single descending aorta, as found in the adult. The aorta gives off
dorsal, lateral, and ventral branches, some of which persist as adult vessels. Aortic arches become carotid, subclavian,
arch of the aorta, and pulmonary arteries.
common
carotid a. aortic
Disposition of Aortic Arches: arch 3
Only the third, fourth, and sixth aortic arches internal
carotid a. dorsal
become adult vessels. The first two arches degenerate and
the fifth arch is rudimentary or absent. external aorta
carotid a.
Each third aortic arch becomes an internal
carotid artery. Proximaly the third arch forms a com- degenerating
mon carotid artery. The dorsal aorta degenerates between dorsal aortic
aorta arch 4
the third and fourth aortic arches. Consequently, the third arch
supplies the head and the fourth arch supplies more caudal aortic
ductus
regions. The external carotid artery buds from the third arch. arteriosus
arch 6
The left fourth aortic arch becomes the adult
pulmonary a. right 7th
arch of the aorta. The right fourth aortic arch becomes the intersegmental a.
proximal part of the right subclavian artery as the distal connec- left 7th
tion between the arch and the dorsal aorta normally degener- intersegmental a. degenerating
descending aorta right dorsal aorta
ates. (Persistence of a connection between the fourth aortic arch
and the descending aorta results in compression of the esopha-
gus, accompanied difficult swallowing and an enlarged esopha- Aortic Arches 3, 4, 6
gus cranial to the compression.) (Dorsal View)

The proximal part of each sixth aortic arch becomes a pulmonary artery. The distal part of the
arch degenerates on the right side but persists as ductus arteriosus on the left side.

26
 Note: The ductus arteriosus shunts blood from the pulmonary trunk to the aorta.
The shunt allows the right ventricle to be exercised in the face of limited ca-
pacity of the lungs to accept & return blood. At birth, ductus arteriosus con-
striction abruptly shifts pulmonary trunk output into the lungs. Eventually, a
ligamentum arteriosum replaces the constricted ductus arteriosus. (A persistent
ductus arteriosus results in a continuous murmur during both systole and diastole.)

Subclavian & Vertebral arteries:

Each dorsal aorta gives off intersegmental arteries that pass dorsally between somites. Bilaterally, the seventh
cervical intersegmental artery becomes the distal portion of the subclavian artery.
Intersegmental arteries cranial to the seventh cervical form the vertebral artery (by anastomosing with one an-
other and losing connections to the aorta via degenertion). Intersegmental arteries caudal to the seventh cervical become
intercostal and lumbar arteries.
As the heart shifts caudally from the neck to the thoracic cavity, positions of aortic arch arteries are changed
relative to the heart. In particular the subclavian arteries becomes transposed from a position caudal to the heart to a
cranial position.

Branches of Dorsal Aortae:

Right and left vitelline arteries arise from right and left dorsal aortae, respectively, to supply the yolk sac. The
right vitelline artery becomes the cranial mesenteric artery. The left vitelline artery normally degenerates. (Incomplete
degeneration of the left vitelline artery can result in a fibrous band that may cause colic by entrapping a segment of intes-
tine.)
Each dorsal aorta terminates in an umbilical artery that supplies blood to the allantois. In the adult, umbilical
arteries persist proximal to the urinary bladder and degenerate distal to the bladder. External and internal iliac arteries
develop as outgrowths of the umbilical artery.

Veins:
The sinus venosus receives vitelline veins which drain the yolk sac, umbilical veins which
drain the allantois, and cardinal veins which drain the embryo. The transition from embryonic to
adult venous patterns involves the formation of new veins, anastomoses between veins, and the se-
lective degeneration of embryonic segments.
Cranial Vena Cava
Note: Recall that venous return is shifted Development (Dorsal View)
to the right side and the right sinus
external
venosus is incorporated into the wall jugular v.
L. sub- R. sub-
of the right atrium. The left sinus
calavian calavian
venosus is reduced and becomes v. v.
coronary sinus. brachio-
cephalic vv.
Cranial Vena Cava Formation:
Each cranial cardinal vein becomes the adult internal degenerated
jugular vein. The much larger external jugular and subclavian left cranial
veins arise by budding from the cranial cardinal vein. cardial v.
An anastomotic vein develops and runs from left to anastomotic cranial
right cranial cardinal veins, shifting venous return to the right branch vena cava
side and becoming left brachiocephalic vein. The caudal
segment of right cranial cardinal vein along with the right
common cardinal vein becomes the cranial vena cava. (Failure caudal
of the anastomotic vein to develop results in a double cranial coronary
sinus right atrium vena cava
vena cava, the typical condition in rats and mice.)
27
Caudal Vena Cava and Azygos Vein:
Each caudal cardinal vein gives rise to supra-cardinal and sub-cardinal veins with extensive anastomoses among
all of the veins. These venous networks, located in intermediate mesoderm, supply embryonic kidneys and gonads.
Selective segments of particularly the right subcardinal venous network, including an anastomosis with the
proximal end of the right vitelline vein form the caudal vena cava.
The azygos vein develops from the supracardinal vein as well as the caudal and common cardinal veins of the
right side (dog, cat, horse) or the left side (pig) or both sides (ruminants). The azygos vein will drain into the cranial vena
cava (or right atrium) on the right side and into the coronary sinus on the left side.

Portal Vein and Ductus Venosus:

heart atrium
Proximally, vitelline veins form liver sinu- common sinus
soids as the developing liver surrounds the veins. cardianl v.
venosus
Anastomoses develop between right and left vitel-
line veins, and enlargement/atrophy of selective
anastomoses and right/left segments of vitelline caudal
cranial
cardinal v.
veins gives rise to the portal vein. cardinal v.
Umbilical veins, also engulfed by the de-
liver
veloping liver, contribute to the formation of liver degenerating
sinusoids
sinusoids. Within the embryo, the right umbilical segment
vein atrophies and the left conveys placental blood right
umbilical LIVER
to the liver. Within the liver, a shunt, the ductus ve-
v.
nosus, develops between the left umbilical vein and
left
the right hepatic vein which drains into the caudal vitelline v.
umbilical v.
vena cava. FOREGUT
Postnatally, the left umbilical vein becomes the
round ligament of the liver located in the free edge of the Vitelline & Umbilical Veins
(Ventral View)
falciform ligament.

Pulmonary Veins:
These develop as outgrowth of the left atrium. The initial growth divides into left and right branches, each of
which subdivides into branches that drains lobes of the lung. Pulmonary branches become incorporated into the wall of
the expanding left atrium. The number of veins entering the adult atrium is variable due to vein fusion.

Note: Because a fetus is not eating and because the placenta is able to detoxify
blood, it is desirable for venous return to bypass fetal liver sinusoids via the
ductus venosus, a shunt that diverts blood to systemic veins.
Postnatally, however, a continuing portosystemic shunt allows toxic
digestive products to bypass the liver. These toxic agents typically affect the
brain resulting in neurologic disorders at some time during life.
A portosystemic shunt can be the result of a persistent ductus venosus or
a developmental error that results in anastomosis between the portal vein and
the caudal vena cava or the azygos vein. Since adult veins are established by
patching together parts of embryonic veins, it is not surprising that mis-con-
nections arise from time to time.

28
Lymphatics:

Lymph vessel formation is similar to blood angiogenesis. Lymphatics begin as lymph sacs in
three regions: jugular (near brachiocephalic veins); cranial abdominal (future cysterna chyla); and iliac region. Lym-
phatic vessels (ducts) form as outgrowths of the sacs.
mesenchyme
Lymph nodes are produced by localized mesoder-
mal invaginations that partition the vessel lumen into sinu- lymph duct lumen
sinusoid
soids. The mesoderm develops a reticular framework within which
lymphocytes accumulate. The spleen and hemal nodes (in ruminants) mesodermal
develop similar to the way lymph nodes develop. invagination
Lymph Node Formation

At birth... Three In-Utero Adjustments

Stretching umbilical arteries re- ductus
sults in arterial constriction and reduced arteriosus
aortic arch
fetal blood flow to the placenta.
pulmonary trunk
Reduced venous return through the L
(left) umbili- cal vein and ductus foramen ovale atrium
venosus
latter to gradually
allows theclose (over a period R
atrium
of days). caudal vena cava

Increased oxygen concentration

in blood triggers constriction of the duc- ductus
venosus
tus arteriosus which, over time, is gradu-
aorta
ally converted to a fibrous structure, the
ligamentum arteriosum. liver

The increased blood flow to the lungs umbilical v.

and then to the left atrium equalizes portal v.
pressure in the two atria which results
in closure of the foramen ovale.

umbilical aa.

29
 Digestive System
NOTE: The digestive system consists of the: mouth (oral cavity); pharynx; esophagus; stomach; small
intestines; colon and cecum; rectum; anal canal; and the liver, pancreas, and salivary glands.

Development of a head process and tail process, including the foregut midgut hindgut
ventral merger of lateral body folds, transforms splanchnopleure into a
foregut and a hindgut, leaving a midgut region that is continuous with pharynx
the yolk sac.
cloaca
NOTE: Foregut becomes pharynx, esophagus, stomach, cranial duode-
num, and liver and pancreas. Midgut becomes the remaining small
intestines, cecum, ascending colon, and part of the transverse yolk allantois
colon. Hindgut becomes transverse and descending colon and a sac
cloaca which forms the rectum and most of the anal canal.
In the abdomen, derivatives of the foregut, midgut, and hindgut
are those structures supplied by the celiac, cranial mesenteric, and
caudal mesenteric arteries, respectively.

Endoderm gives rise to the epithelial lining of the digestive tract, while splanchnic mesoderm
forms connective tissue and smooth muscle components of the digestive tract wall; except that ecto-
derm forms the epithelial lining of the proctodeum (caudal end of anal canal) and stomadeum (mouth
& salivary glands — parotid, zygomatic, labial & buccal).

Pharynx... stomach pancreas

The adult pharynx is a
common respiratory-digestive
chamber. Initially, the phar- trachea liver gall
ynx is bounded cranially by bladder

pharyngeal Alimentary
an oropharyngeal membrane.
The membrane degenerates
early, allowing the pharynx to
pouches Canal midgut
communicate with the oral and
diverticulum
nasal cavities, and enabling
cecum
migration of tongue muscula-
ture into the oral cavity.
Although the adult pharynx has a smooth wall, pharyngeal
pouches appear during development. The pouches give rise to several allantois
structures, two of which retain continuity with the pharyngeal cavity
(auditory tube and fossa of the palatine tonsil). A midline evagination
of the floor of the pharynx gives rise to the larynx, trachea and lungs. cloaca

Esophagus...
The esophagus develops from foregut, caudal to the pharynx.
Its principal morphogenic development is elongation.
Skeletal muscle associated with esophagus & pharynx is derived from somites that migrate to
the branchial arches IV-VI (innervation is from vagus nerve). Esophagus is coated by skeletal muscle throughout its
length (dog, ruminants), to the diaphragm (pig), to the mid-thorax (cat, horse, human), or not at all (avian).
30
 SIMPLE STOMACH DEVELOPMENT
LEFT DORSAL VIEW RIGHT
esophagus
esophagus

lesser
✪
curvature
dorsal border

fundus
stomach
duodenum
stomach

Rotated
✪ Long Axis
Transverse
Left greater curvature
duodenum
Stomach (simple stomach)...
Most domestic mammals have a simple stomach (in contrast, ruminants have a complex stom-
ach with multiple compartments). The simple stomach develops from a tubular segment of foregut
that undergoes the following morphogenic changes:
• growth is more rapid dorsally than it is ventrally; the tube becomes convex dorsally (the
future greater curvature) and concave ventrally (future lesser curvature);
• the tube rotates 90° to the left (dorsal faces left & ventral faces right);

• the long axis becomes transverse as growth of the liver pushes the cranial end of the
stomach to the left side (the greater curvature drops ventrally when the stomach is filled);
— growth along the cranial aspect of the greater curvature is greater than along
the caudal aspect — this produces a duodenum
fundus region (to the left); esophagus
— endoderm, which forms the epithelial omasum
lining of the stomach, differentiates
into cells types that vary regionally abomasum
among species. reticulum
rumen
Ruminant stomach... Rumen
The ruminant stomach consists of three compart- Development
ments lined by stratified squamous epithelium (rumen,
esophagus
reticulum, and omasum) and one glandular compart-
ment (abomasum). The early development of the rumi-
nant stomach is the same as the simple stomach. rumen (dorsal sac)
The rumen develops as an expansion of the fundus,
and a caudoventral pocket of the developing rumen rumen
forms the reticulum. The omasum develops as a bulge (ventral sac)
along the lesser curvature. The rest of the stomach
becomes abomasum. Later in development the rumen reticulum
abomasum
is “flipped” caudally so it comes to lay on top of the
abomasum with the reticulum situated cranially.

omasum duodenum
31
 Rotation of Gut Around Cranial Mesenteric A.
(left side view)
stomach cranial mesenteric artery

stomach

cecum

cecum
start
yolk
sac stomach

cecum

360 degrees
180 degrees

Intestinal tract...
NOTE. The intestinal tract consists of: duodenum (descending & ascending), jejunum, ileum, colon (ascending,
transverse, & descending). cecum (diverticulum at the beginning of the colon), rectum, and anal canal.

In addition to elongation, the following morphogenic events occur:

— elongation of the midgut (where the yolk sac is attached) causes the midgut to form a loop
that herniates into the coelom of the umbilical stalk;
— the loop rotates approximately 360° around the cranial mesenteric artery (former right
vitelline a.), the rotation is clockwise as viewed dorsally (freedom to rotate is the result
of lost yolk sac attachment and elongation of the cranial limb of the loop);
— the caudal limb of the loop develops a diverticulum, the future cecum. As the embryo
grows, the loop returns to the embryonic coelom (abdominal cavity).

NOTE:
The intestinal tract and esophagus normally undergoes atresia (occlud-
ed lumen) during development as a result of epithelial proliferation. The
atresia is temporary. Recanalization occurs by formation of vacuoles that
coalesce to form the ultimate lumen. Persistent atresia (failure to re-cana-
lize) or stenosis (narrow lumen) is a congenital anomaly that can occur at
localized sites anywhere along the esophagus or intestines.
Failure of the yolk sac to detach from the midgut (jejunum) can result
in either a diverticulum of the jejunum, a fistulous (hollow) cord to the
umbilicus, or a fibrous connection between the jejunum and umbilicus.
Each of these can be a source of colic.

Additional intestinal events in some species...

a secondary loop (of ascending colon) forms distal to the cecum (see following illustration):
• in pig and ruminant—the secondary loop coils (forming the spiral colon);
• in horse—the secondary loop bends on itself; also the cecum enlarges so that the proximal colon
is incorporated within the cecum.
32
 Ascending Colon Loop
(right side view)
descending cranial mesenteric a.
colon
descending
porcine
duodenum
ascending colon
cecum
bovine

stomach
ileum

equine
jejunum

Cloaca...
The hindgut terminates in a cloaca, i.e., a chamber that communicates with the digestive,
urinary and genital systems (the cloaca persists in adult birds, reptiles, & amphibians). The allantois
evaginates from the hindgut at the cranial end of the cloaca. The caudal wall of the cloaca, which is
formed by endoderm apposed to surface ectoderm, is designated cloacal membrane.

Rectum: The rectum is formed when a mesenchyme

anal
partition (urorectal septum) divides the cloaca into dorsal
canal
and ventral chambers. The dorsal chamber, which is con-
rectum
tinuous with the hindgut, becomes the rectum and most of
urorectal
the anal canal. The ventral chamber, the urogenital sinus, is septum
continuous with the allantois.
allantois
The urorectal septum grow caudally and divides the
cloacal membrane into an anal membrane dorsally and a urogenital cloacal
sinus membrane
urogenital membrane ventrally. The membranes subsequent-
ly disintegrate in normal developement. Cloaca Divisions

Anal canal: The cranial part of the anal canal (most of the canal) is formed with the rectum;
this part of the anal canal is lined by a mucosal epithelium derived from endoderm. The caudal part
of the anal canal (caudal to an anocutaneous line) is lined by stratified squamous epithelium. It forms
as follows:
— tissue surrounding the anal membrane grows caudally creating a depression
called the proctodeum; when the anal membrane degenerates, the
proctodeum becomes incorporated into the anal canal (atresia ani or intact
anal membrane is a congenital anomally);
— in carnivores, lateral diverticula of proctodeum ectoderm become anal sacs.
NOTE: The urinary bladder develops from the cranial part of the urogenital sinus
and the proximal end of the allantois.

33
Liver...
The liver arises as an hepatic diverticulum of endoderm from the region of foregut that will
become descending duodenum. The diverticulum gives rise to multiple branches that become:
hepatic ducts, cystic duct and the pancreatic duct.
Continued growth and branching of hepatic duct primordia form the lobes of the liver. A gall
bladder develops at the end of the cystic duct. The initial part of the hepatic diverticulum from which
the various branches arose becomes the bile duct.
The hepatic diverticulum grows within ventral mesogastrium (lesser omentum). (The diverticulum temporarily
penetrates the future diaphragm (septum transversum) which contributes connective tissue to the liver.)
The hepatic diverticulum originates ventrally but differential growth of the duodenal wall results in the bile duct
entering the duodenum dorsally, with the pancreatic duct on the major duodenal papilla.

Pancreas...
The pancreas originates as two separate endoderm diverticula, each of which elongates,
branches, and then forms acini in typical glandular fashion. One diverticulum arises ventrally as a
bud of the hepatic diverticulum; it forms the pancreatic duct and right lobe of the pancreas. The other
diverticulum arises dorsally from the duodenum (minor duodenal papilla) and forms the accessory
pancreatic duct and the left lobe of the pancreas.
As the right and left lobes cross one another during development, they fuse to from the body
of the pancreas; also, the duct systems anastomose to form a common system. The endocrine (islet)
cells of the pancreas also develop from the endoderm of the diverticula.
NOTE: One of the two pancreatic ducts will be smaller that the other and may even disappear.
Which one is destined to become smaller or absent depends on the species.

Pancreas & Liver Development

pancreas
(left lobe) pancreas
(right lobe)

duodenum
gall
bladder

hepatic
diverticulum
hepatic ducts

Avian...
The avian digestive tract features:
— a crop, which develops as a diverticulum of the esophagus;
— a two-compartment stomach:
1] proventriculus (glandular stomach) and
2] ventriculus or gizzard (stratified squamous epithelium and
heavy muscles for grinding);
— a pair of ceca;
— a cloaca which opens externally by means of a vent.

34
Mesenteries...
v Mesenteries are formed by splanchnic mesoderm when the embryonic gut is created as the
embryo assumes a tubular shape.
Splanchnic mesoderm is separated from somatic mesoderm by the embryonic coelom. Meso-
derm lining the coelom transforms into serous membrane, making the coelom a serous cavity.
Mesoderm
Caudal to the pharynx (head pro-
= somite neural tube
cess), dorsal and ventral “mesenteries” of
= intermediate notochord
the esophagus persist as mediastinum in = lateral fore gut
the thorax.
Lateral
In the abdomen, a dorsal mesen-
Body
tery is continuous, but a ventral mesen- Folds
tery is absent caudal to the stomach and mbryonic
e
cranial to the cloaca. coelom
mesentery
The dorsal mesentery becomes:
greater omentum, mesoduodenum, mes-
entery (mesojejunum and mesoileum), somatopleure extra-embryonic
mesocolon, and mesorectum. splanchnopleure yolk coelom
The original dorsal mesogastrium sac
elongates greatly as it forms greater
omentum. The left lobe of the pancreas develops within the dorsal portion of the greater omentum. The spleen develops
within the greater omentum from blood vessels that accumulate in the vicinity of the greater curvature of the stomach.
As the midgut elongates and rotates around the cranial mesenteric artery, portions of the me-
sojejunum and mesoileum come into contact near the dorsal body wall and fuse, forming the root of
the mesentery. Parts of the mesoduodenum and mesocolon also fuse to the root the mesentery.
The ventral mesentery, in which the liver develops, becomes the lesser omentum and coro-
nary and falciform ligaments of the liver. Caudally, ventral mesentery becomes median ligament of
the urinary bladder.

Mesenteries (lateral view)

mesentery
mesocolon

spleen

stomach
lesser
omentum cloaca
cecum
liver

falciform ligament
umbilicus

35
 Respiratory System
The respiratory system consists of the nasal cavity, pharynx, larynx, trachea and lungs. The
lining of the nasal cavity is derived from ectoderm; the lining of the rest of the respiratory system
comes from endoderm.

Summary of Nasal Cavity Development: (details given later in Face Development lecture)
• initially, bilateral nasal (olfactory) placodes appear (the placodes are ectodermal thicken-
ings at the ventral tip of the frontonasal prominence)
• placodes become nasal pits by outward growth of the surrounding medial and lateral nasal
processes of the frontonasal prominence
• continued outgrowth of medial & lateral nasal processes elongates the nasal pits and trans-
forms them into a nasal cavity
• right and left medial nasal processes fuse to form a primary palate (incisive bone & rostral
upper lip) and a nasal septum; lateral nasal processes become nose cartilage and nasal & lacrimal
bones
• formation of the
Palate Formation
secondary palate divides nasal pit nasal septum
a common naso-oral space
primary palate concha
into three separated cavities
(right & left nasal cavities nasal cavity
nasal cavity
and the oral cavity); also, nasal septum secondary
the secondary palate divides patate
the pharynx into three com- secondary tongue
partments (nasopharynx, patate oral cavity
oropharynx, & laryngophar- Transverse View
Ventral View
ynx)
• conchae (scrolls of thin bone covered by mucosa) arise as cartilaginous ridges from bones
of the nasal cavity wall
• paranasal sinuses (diverticula of the nasal cavity) develop post-
natally. pharynx

Larynx, Trachea and Lungs: L-T groove

These respiratory structures originate as an evagination of endo- CUT

derm along the floor of the pharynx. The evagination is designated the
laryngotracheal groove.
From lateral walls of the laryngotracheal groove, ridges grow L-T tube
medially, and fuse along the midline, establishing a tracheoesophageal
septum. The septum separates a laryngotracheal tube (future trachea &
lung buds) from the esophagus. Laryngo-Tracheal
The larynx develops rostrally, where the lumen of the groove re- Groove
tains communication with the pharynx. (ventral view)
36
 Larynx:
The wall of the larynx originates from growth of bilateral laryngeal swellings (future arytenoid,
thyroid, & cricoid cartilages) and a rostral epiglottal swelling. The swellings border the persistent
laryngeal opening (between laryngotracheal groove and the pharynx). A diverticulum of the lateral
laryngeal wall produces a lateral ventricle & vocal fold (not in cats & cattle).
Pharyngeal arch splanchnic mesoderm forms laryngeal swellings and cartilages. Laryngeal mus-
cles develop from somitomeres that migrate to pharyngeal arches: IV (cricothyroideus m. innervated
by the vagus n. cranial branch) and VI (other muscles innervated by the vagal recurrent laryngeal n.)

epiglottal swelling proximal tongue

left laryngeal swelling distal swellings
epiglottis

I
I vocal
fold
piriform aryepiglottic
II II
recess fold
laryngeal
III III left opening
b ranchial pharyngeal arytenoid
( visceral) I V pouches cartilage
c ricoid
arches I-IV thyroid ca rtilage
I-IV IV cartilage

Dorsal View of Floor of Pharynx (roof removed) Dorsal View of Larynx

Trachea and bronchi:

The laryngotracheal tube grows caudally into splanchnic mesoderm located ventral to the phar-
ynx. The mesoderm contributes cartilage and connective tissue and endoderm contributes respiratory
epithelium to the developing trachea. Tracheal elongation Porcine trachea
shifts bronchi caudally into the thorax. Early tracheal
The blind, caudal end of the tube develops bi-lobed bron- Stage bronchus
chial buds which grows to form the future principal bronchi.
Outgrowths of each principal bronchus form future lobar
bronchi, each of which gives rise to outgrowths that become
future segmental bronchi, each of which gives rise to more Later Stage
than a dozen additional bronchial branches. The smallest
branches are bronchioles. They give rise to lung terminal sacs principal
bronchus
and alveoli.
The bronchial branchings continue to occur throughout
the fetal period and into the postnatal period.
lobar
NOTE: Generally in domestic mammals, the right principal bronchus bronchus
divides into four lobar bronchi (to cranial, middle, caudal &
accessory lobes), while the left gives rise to two lobar bronchi segmental
(to cranial & caudal lobes). b ronchus

There are right side exceptions: the horse lacks a middle lobe;
(humans lack an accessory lobe;) in ruminants and swine the Bronchial Development
right cranial lobe is supplied by a tracheal bronchus. (Dorsal View)
37
Lungs:
Continued branching of the bronchial tree results in lung tissue occupying more and more of
the pleural cavity, coated by visceral pleura. The endoderm-lined bronchial tree grows into splanch-
nic mesoderm which forms the cartilage, fascia, smooth muscle, and vessels of the lung.
Initially, bronchiole-lung branches are solid cores of cells that grow into splanchnic meso-
derm (growth is like exocrine gland growth into mesoderm). Eventually, terminal branches become
hollow, dilated, and sac-like with endoderm becomes a thin epithelium (terminal sacs). Alveoli are
created by the formation of septae that partition the terminal sacs.
Some endodermal alveolar cells become cuboidal rather than flat and produce a phospholipid
surfactant that reduces surface tension and thus facilitates alveolar expansion (as opposed to alveolar
collapse). Fetal lungs contain fluid that facilitates the breathing movements that take place in utero to
prepare for postnatal respiration. At birth, lung fluid drains or is absorbed as air is breathed.

NOTE: Species differ in degree of lung maturity at birth. Also, within a single lung, dis-
tal regions are less mature than proximal ones. Formation of new alveoli occurs
post-natally to a considerable extent in all mammals. Subsequently, lung growth
is due to hypertrophy (increased size) of alveoli and air passageways.

Alveolar Formation
future alveolus
capillary
septum

terminal
sac

squamous
epithelium

terminal
cuboidal
epithelium sac

septum future alveolus

38
 Urinary System
Intermediate mesoderm

lateral mesoderm: somite neural ectoderm

splanchnic NOTE: Intermediate mesoderm
groove
somatic is situated between somites and
lateral mesoderm (somatic and
splanchnic mesoderm bordering
the coelom). All mesoderm is
derived from the primary mesen-
intermediate mesoderm endoderm chyme that migrated through the
notochord coelom
(becomes urogenital ridge) primitive streak.

Intermediate mesoderm (plus adjacent mesothelium lining the coelom) forms a urogenital
ridge that consists of a laterally-positioned nephrogenic cord (which forms kidneys & ureter) and a
medially-positioned gonadal ridge (for ovary/testis & female/male genital tract formation).
Interme- diate mesoderm also gives rise to adrenal cortex.
NOTE: Urine production essentially requires an increased capillary surface area
(glomerulus), epithelial tubules to collect plasma filtrate and extract
desirable constituents, and a duct system to convey urine away from the body.

Kidneys
mesonephric duct
Three kidneys de-
velop from each nephrogenic pr metanephros
cord. They develop chrono- onephros
mesonephric tubules
logically in cranial-caudal
mesonephros
sequence, and are designated
pro—, meso—, and meta—, Nephrogenic Cord (left)
respectively. cloaca
The pronephros and mesonephros develop similarly: the nephrogenic cord undergoes seg-
mentation, the segments become tubules, and the tubules drain into a duct. Eventually the tubules
disintegrate. spinal ganglion

1] Pronephros—consists of (7-8) primitive

tubules which fuse to form a pronephric duct that
neural
grows caudally and terminates in the cloaca. The tube
tubules soon degenerate, but the pronephric duct somite
persists as the mesonephric duct. (The pronephros is notochord
not functional, except in sheep.) mesonephric
tubule
NOTE aorta
The mesonephros is the functional kidney for fish body
wall
and amphibians. The metanephros is the function-
al kidney of reptiles, birds, & mammals. mesentery coelom

Although kidneys may become functional in-ute- glomerulus mesonephric

gut duct
ro, they are not essential because the placenta is
capable of removing toxic agents from fetal blood.
39
 2] Mesonephros—consists of (70-80) tubules induced to form by the mesonephric duct
(former pronephric duct). One end of each tubule surrounds a vascular proliferation (glomerulus)
produced by a branch of dorsal aorta. The other end communicates with the mesonephric duct. The
mesonephros eventually degenerates, except for a few caudal tubules and the mesonephric duct
which become testicular channels and epididymis/ductus deferens in the male. (The functional develop-
ment of the mesonephros is inversely related to the numbers of tissue layers in the placenta.)

3] Metanephros—becomes the adult kidney and ureter of metanephrogenic

mass
mammals, birds, and reptiles. The metanephros forms in the pelvic
region and, by differential growth, it “ascends” cranially into the
abdomen. It is lobulated initially and subsequently becomes smooth in
allantois
many species. The metanephros originates from two sources:
ureteric
— a ureteric bud (induced by neural tube) grows out of the meso- bud
nephric duct in the region of the cloaca; the bud eventually develops urorectal
into the ureter, renal pelvis, and numerous collecting ducts; septum
— metanephrogenic mass is the caudal region of the nephro- cloaca
genic cord. Note: When the ureteric bud grows into the mesoderm, it induces the
metanephrogenic mass to develop; in turn, the mass induces the cranial end of the renal pelvis
ureteric bud to differentiate into renal pelvis and collecting tubules—these, in turn, ductus
induce the metanephrogenic mass cells to form nephrons. deferens

The metanephrogenic mass forms nephrons in the following manner:

urachus
• adjacent to collecting tubules, mesodermal cells proliferate to
form cell cords that canalize and elongate, becoming S-shaped, meta-
nephric tubules and eventually nephrons; ureter
• one end of each metanephric tubule establishes communica- urinary
bladder
tion with a collecting tubule; the other end of the tubule expands and
surrounds a capillary glomerulus (forming a glomerular capsule);
• between the two ends, each metanephric tubule differentiates urethra rectum
into regions (proximal segment, thin loop, and distal segment) charac- Metanephros
teristic of a nephron

cell cord glomerulus

mesenchyme
hollow cord
future
nephron
metanephric collecting duct
tubule

Nephron
collecting duct Formation collecting
tubule

NOTE: Nephrons develop from deep to superficial in the kidney. Many of the early nephrons subse-
quently degenerate as a normal occurrence. Nephrons continue to form and mature postnatally
(except in the bovine); thereafter, nephrons cannot be replaced if they are damaged.

40
Urinary Bladder and Urethra mesonephric
ureteric bud
duct
The cloaca is divided by a urorectal septum into, dor- urorectal
septum
sally, a rectum & anal canal and, ventrally, a urogenital sinus. rectum
The septum also divides the cloacal membrane into an anal
membrane and a urogenital membrane. The membranes subse- urogenital
sinus
quently degenerate, resulting in an anus and urogenital orifice,
urachus
respectively.
Cranially, the urogenital sinus opens into the urachus,
the intra-embryonic stalk of the allantois. The urogenital sinus may allantois
cloacal
be divided into a pelvic (cranial) region and a phallic (caudal) region. membrane

Urinary bladder develops from an expansion of the urachus (allantois) and the cranial end
of the urogenital sinus. The expansion incorporates the mesonephric duct (future ductus deferens)
and ureter into the dorsal wall (trigone region) of the future bladder. Differential growth of the dorsal
wall results in the mesonephric duct and ureter having separate openings with the positions of the
openings switched cranio-caudally. (Thus the bladder trigone region originates separately, from mesoderm.)

Urethra develops from the urogenital sinus. The development is gender specific:
In females, the mid region of the urogenital sinus becomes urethra. (The caudal region of the
urogenital sinus become vestibule and vagina arises as an outgrowth of the future vestibule.)
In males, the pelvic urethra develops from the mid region of the urogenital sinus and the
penile urethra develops from elongation of the caudal end of the urogenital sinus.
NOTE: In the fetus, urine is discharged into the allantoic cavity through the
urachus and into the amniotic cavity through the urogenital orifice.

Abnormalities of development include:

• Hydronephrosis (cystic/polycystic kidneys) results from ureteric atresia or from failure of
nephrons to communicate with collecting tubules.
• Patent urachus (urachal fistula) results from a failure of the allantoic stalk to close at birth.
Also, vesicourachal diverticulum (urachus persisting as a blind pouch) is a source of chronic cystitis.
• Ectopic ureter, where the ureter opens into the urethra or vagina instead of the bladder, is a
source of incontinence.

Adrenal Cortex
The adrenal gland consists of an adrenal medulla and an adrenal cortex that are embryologically, histologically,
and functionally different, even though they are combined grossly. The adrenal medulla is derived from neural crest
(ectoderm). The adrenal cortex arises from cells of mesonephric nephrons that dissociate from the nephron and migrate
to the location of the adrenal medulla.

neural crest adrenal adrenal

cells cortex medulla

cortex
primordium
Adrenal Gland
41
 Genital System
Development of genitalia involves transition through an indifferent stage in which gonads,
genital ducts and external features appear the same in both sexes. Most genital anomalies involve
some combination of intersex development.

Gonads
Indifferent stage. Each gonad arises from a gonadal ridge, a thickening of intermediate me-
soderm and overlaying coelomic mesothelium that develops medial to the mesonephric kidney. The
parenchyma of a gonad consists of germ cells and supporting cells:
— supporting cells are derived from invading coelomic mesothelial cells, augmented by cells
from disintegrating mesonephric tubules. The supporting cells form cellular cords (gonadal cords)
that radiate into gonadal ridge mesoderm;
— primordial germ cells arise from yolk sac endoderm; they migrate through the gut wall
and its mesentery to reach the gonadal ridge. Their arrival induces further gonadal development:
Germ cells proliferate and migrate into cellular cords to become surrounded by supporting
cells (germ cells that fail to enter a cellular cord undergo degeneration).
seminiferous tubule
migrating germ cells
degenerating mesonephric germ cell
germ cell
mesonephric tubule
duct & tubules

mesonephric duct

mesothelial cords
mesonephric duct
paramesonephric duct
rete testis &
Indiffernt efferent ductules
paramesonephric follicle
Gonad
duct Ovary Testis

Testis. The cellular cords, now called seminiferous cords, hypertrophy. Germ cells within
seminiferous cords differentiate into spermatogonia and become dormant. (Deep cellular cords lack-
ing germ cells become tubules of the rete testis, located centrally in the testis). At puberty, the cords
become canalized, forming seminiferous tubules and spermatogonia initiate spermatogenesis.
Supporting cells that form walls of the seminiferous cords differentiate into sustentacular
(Sertoli) cells which secret inhibitory factors that suppress spermatogenesis (and female duct devel-
opment). Supporting cells outside seminiferous cords become two populations of interstitial cells—
one population produces androgens immediately, the other population delays androgen production
until sexual maturity. Androgens stimulate male genitalia development in the fetus and at puberty.
Coelomic mesothelium covering the testis becomes visceral peritoneum. Mesenchyme deep
to the mesothelium proliferates and becomes tunica albuginea.

NOTE: In ovaries, 90% of the germ cells fail to become incorporated into follicles;
they complete meiosis and degenerate. The onset of meiosis is delayed in em-
bryos of species having longer gestations to reduce germ cell degeneration.
42
 Ovary. The cellular cords that contain germ cells undergo reorganization so that individual germ
cells become isolated, each surrounded by a sphere of flat supporting cells—forming primordial fol-
licles. Follicle and germ cell proliferation is completed before birth. Germ cells (oogonia) differenti-
ate into primary oocytes that commence meiosis, but remain in prophase of Meiosis I until ovulation
following puberty. The full allotment of primary oocytes is present in the neonatal ovary.

Genital ducts, accessory glands, and ligaments

Indifferent stage. Both sexes have male (mesoneph-
ric) and female (pramesonephric) genital ducts and a Transverse Section through
urogenital sinus. The mesonephric (Wolffian) duct persists Urogenital Ridge
after the mesopnephros disintegrates. A parameso-
nephric (Mullerian) duct develops along the ventrolateral mesonephric
tubules
surface of the mesonephros. It begins as a groove at
the coelomic surface. The edges of the groove merge to
form a core of cells that canalize and elongate.
Which duct system develops, is determined by
testicular hormones. Male duct development requires gonad
paramesonephric
testosterone (produced by interstitial cells). The testis duct coelomic
mesonephric
(sustentacular cells) also releases an inhibitory hormone duct mesothelium
that suppresses female duct development.

Female. In the absence of testosterone, mesonephric ducts fails to develop (histologic remnants
may be found in the wall of the vestibule).
The cranial region of each paramesonephric
duct remains open and forms the future uterine degenerating
Female
mesonephros
tube. Caudal to the level of the inguinal fold (gu- Genital
bernaculum), each paramesonephric duct becomes Duct
a uterine horn. Further caudally, the bilateral
paramesonephric ducts shift medially and fuse into
a single tube that ends blindly in contact with the ovary
urogenital sinus. The fused ducts become uterine broad ligament
(urogenital fold)
body, uterine cervix, and the cranial third of the uterus
vagina.
NOTE: The degree of fusion of paramesonephric ducts is species dependent. Among domestic animals fu-
sion is greatest in the horse and least in carnivores. In primates (women) fusion normally produces
a uterine body without horns. In contrast, rodents and the rabbit have a double uterus (two cervices
enter a single vagina). Monotremes and many marsupials have a double vagina (no fusion at all).

Vaginal Development uterine

The vagina has a dual origin. The cranial one-
(lateral view) body
third comes from fused paramesonephric ducts.
lumen of fused
pramesonephric urethra The caudal two-thirds comes from the vaginal
ducts plate, a solid tubercle that grows outward from
cervix the urogenital sinus at the site of contact between
vaginal the urogenital sinus and the fused paramesoneph-
lumen ric ducts. Degeneration of the center of the solid
vaginal
plate tubercle creates the vaginal lumen. A hymen may
hymen persist where the vagina joins urogenital sinus.
urogenital
sinus vestibule The urogenital sinus forms the vestibule.
43
 efferent ductules
rete testis
Male. Paramesonephric ducts regress due seminiferous
to an inhibitory hormone produced by the testis tubule
(sustentacular cells). Duct remnants may be found in
the adult male horse (uterus masculinus).
About a dozen mesonephric tubules are
converted to efferent ductules (they already com-
municate with the mesonephric duct but must establish tunica
albuginea
communication with the rete testis). The cranial
region of the mesonephric duct undergoes
extensive elongation and coiling to become the Male Gonad
epididymis; the remainder of the duct enlarges & Ducts
and becomes ductus deferens. The mesonephric (left side)
duct empties into the urogenital sinus which
becomes pelvic and penile urethra. epididymis degenerating
Glands. Prostate and bulbourethral glands paramesonephric
duct
develop in typical gland fashion from evagina-
tions of urogenital sinus endoderm. (Vestibular
glands are female homologues of male bulbourethral
glands.) Each vesicular gland (seminal vesicle) gubernaculum
arises as an epithelial evagination from the cau-
dal region of the mesonephric duct (mesoderm). ductus
Gland smooth muscle comes from surrounding deferens
mesenchyme.
Ligaments. When the mesonephros degenerates, it leaves behind a gonad and duct system sus-
pended by a genital fold. That fold becomes male or female genital ligaments.
In females, the genital fold becomes: suspensory ligament of the ovary , mesovarium, mesosal-
pinx, and the cranial part of the mesometrium. The caudal part of the mesometrium is formed by the
tissue “shelf” that accompanies each paramesonephric duct when it shifts medially to fuse with its
counterpart. In males, the genital fold becomes mesorchium and mesoductus deferens.
The inguinal fold is a caudal extension of the genital fold that runs along the body wall and into
the inguinal region. It becomes the proper ligament of the ovary and round ligament of the uterus in
females. In males, it gives rise to the gubernaculum of the fetus which subsequently in the adult be-
comes the proper ligament of the testis and ligament of the tail of the epididymis. These derivatives
of the inguinal fold preclude closure of the body wall, and thus are responsible for formation of the
inguinal canal and vaginal process (evagination of the coelom).

Descent of the Gonad

In both sexes, there is a caudal shift of the gonad from its original position. The shift is due to
elongation of the body and a variable degree of retention by the inguinal fold derivative that indirect-
ly attaches to the gonad. In females, the ovary remains intra-abdominal and the extent of caudal shift
is species dependent (e.g., slight in the bitch vs. descent to the pelvis in the cow). In males the testis descends
to the inguinal region.
Testicular descent. The gubernaculum originates as a condensation of the mesenchyme within
each inguinal fold. Under the influence of gonadotropins and testicular androgens, the gubernaculum
accumulates fluid and become a gel mass as large in diameter as a testis. The swollen gubernaculum
enlarges the future inguinal canal. Subsequent outgrowth of the scrotal wall and dehydration of the
gubernaculum passively pulls the testis to the inguinal canal, where a sudden increase in intra-ab-
dominal pressure can pop it through the canal into the scrotum.
44
 External Genitalia
Indifferent stage. External genitalia are derived from three different swellings (mesoderm
proliferations) in the inguinal region:
• bilateral urogenital folds that border the urogenital orifice, the folds elongate as the orifice
elongates ventrally (Urogenital folds are formed when the urorectal septum divides the cloaca. Cloacal folds become
urogenital folds and anal folds surrounding the respective orifices.)
• a genital tubercle, located at the ventral commissure of the urogenital folds;
• bilateral genital (labioscrotal) swellings are located lateral to the urogenital swellings (in
domestic mammals these develop only in males, unlike humans where the swellings develop in both
sexes and form major labia in women).

Human External Genitalia

anus Development anus

genital
labium major swelling scrotum
hymen
labium urogenital
vagina minor sinus
urethral vestibule urogenital fold penis
opening (phallus)
genital
tubercle prepuce
clitoris glans
urethral opening
Indifferent
Female Stage Male

Female. The urogenital orifice becomes the vulval cleft, which opens into the vestibule (uro-
genital sinus). The genital tubercle becomes the clitoris (generally not well developed in domestic
animals). The urogenital folds enlarge, overgrow the genital tubercle, and become labia of the vulva.
Genital swellings disappear in female domestic animals.

Male. Growth at the base of the genital tubercle forms an elongate phallus. The original tu-
bercle becomes glans at the tip of the phallus. The urogenital orifice (sinus) elongates along with the
phallus forming a urogenital groove. The penile urethra is created when the groove closes by medial
merger of urogenital folds in proximal to distal sequence.
The opening of the distal end of the penile urethra, within the original genital tubercle, is
formed by ectoderm invasion and canalization which establishes communication between the ex-
terior and the endodermal penile urethra. Genital tubercle mesenchyme gives rise to penile erectile
tissue, tunica albuginea, muscle, and bone (carnivores).
The prepuce is formed by a ring of ectoderm that invades into the mesenchyme of the free
end of the phallus, dividing tissue into a penis encircled by preputial skin. (Except in the cat, the
phallus of domestic mammals elongates deep to the skin of the ventral body wall.)
Genital swellings enlarge and merge at the midline to form a single scrotum (with two com-
partments). The scrotum initially overlies the gubernaculum and vaginal process caudally in the
inguinal region, but then it shifts cranially (except in the cat and pig).

45
 Mammary Glands

In both sexes, a mammary ridge (line) of thickened ectoderm forms bilaterally from the axil-
lary to the inguinal region. Mammary buds develop periodically along the ridge; elsewhere, mam-
mary ridge ectoderm regresses. Buds determine the number and locations of mammary glands, since
each bud develops into a mammary gland (2, sheep, goat, mare; 4 cow; 8, queen; 10, bitch; 14; sow).
At each mammary bud, ectoderm induces proliferation of underlying mesoderm (teat forma-
tion) and mesoderm induces epithelial cell proliferation. Epithelial cell cords invade underlaying
mesoderm and eventually canalize to form epithelial lined lactiferous ducts. The number of cell cord
invasions and subsequent lactiferous duct systems per teat is species dependent (approximately: 1, sheep,
goat, cow ; 2 mare sow; 6, queen; 12, bitch). In some cases, multiple lactiferous ducts open into a pit (in-
verted nipple) that becomes a nipple following proliferation of underlaying mesoderm.
Commonly, extra buds develop and degenerate, failure to degenerate results in supernumer-
ary teats.

Dog
(ventral view)

mammary mammary
ridge bud

46
 Face, Nasal Cavity, Mouth, &Pharynx
Face:
The face develops from outward growth of tissue located rostral to the pharynx. The lower
jaw and most of the upper jaw are formed by growth of the first pharyngeal (branchial) arch. The up-
per incisor region and the nose and forehead (frontal region) are formed from tissue located rostral to
the neural tube (frontonasal prominence). The development process proceeds as follows:
-the first pharyngeal (branchial) arch grows outward as two processes:
• a lower (mandibular) process grows first and forms the mandible and soft tissue
of the lower jaw (right and left processes fuse to form the mandibular symphysis)
• an upper (maxillary) process grows to form most of the upper jaw (caudal
to the incisor teeth)
- dorsal to each maxillary process, a frontonasal prominence expands outward;
it soon becomes divisible into a frontal prominence (which forms frontal
bone of the forehead) and medial & lateral nasal processes.

Head Process fro ntonasal

(Ventral View) pro minence
pharynx nasal placode
maxillary
stomodeum p rocess
nasal
mandibular
placode
oropharyngeal process
membrane early
(deep wall of
stomodeum)
medial nasal
process lateral
Sagittal al
nascess
Section nasal pit pro
maxillary
nasolacrimal process
groove
mandibular
ranchial
hyoid b rch (I)
branchial a
branchial arch (II)
arches
eye frontal
Lateral prominence
Surface
View
nasal eye
pit nostril
upper mouth
jaw
lower hyoid
jaw apparatus
Three-week old embryo late

47
 Pharyngeal Arches
• Six pairs of pharyngeal (branchial) arches develop, although only the first three are superficially
distinct in mammals. (Arch V atrophies & arch VI merges with arch IV.) Adjacent pharyngeal
arches are separated by pharyngeal clefts (grooves). The external clefts are apposed internally
by pharyngeal pouches.
• All mesenchyme within pharyngeal arches (and within the frontonasal prominence) is ectomesen-
chyme, derived from neural crest. Ectomesenchyme forms intramembranous bone and fascia of
the face and cranium, since these develop from pharyngeal arches. (Bones of the base of the skull
develop endochondrally from mesodermal mesenchyme derived from occipital somites.)
• Skeletal muscle of the head is derived from either somites or somitomeres that migrate into pharyn-
geal arches or the frontonasal prominence. In general, each pharyngeal arch is innervated by one
cranial nerve that supplies all structures derived from the arch.
Note: Somitomeres resemble somites, but they originate from paraxial mesoderm
located rostral to the notochord. There are seven pair of somitomeres. They
give rise to extraocular, masticatory, facial, and some pharyngeal muscles.

Nasal cavity:
Initially, a nasal placode (ectoderm thickening) appears
bilaterally at the rostral end of the frontonasal prominence. Nasal
Subsequent growth of surrounding medial and lateral nasal Processes:
processes forms a nasal pit (bilaterally). Continued growth of
each nasal pit, plus wall erosion, produces a primitive nasal medial
cavity that communicates bilaterally, with the oral cavity. lateral
The bilateral rostral openings of the nasal cavity be-
comes external nares (nostrils) and ectomesenchyme surround-
eye
ing them forms cartilage of the nose. Each lateral nasal process
give rise to alar cartilage of the nose, nasal bone and lacrimal bone. A
nasolacrimal duct is formed by ectoderm along the seam where the lateral
nasal process meets the maxillary process. nasal pit
Fusion of right and left medial nasal processes forms mandibular process
a primary palate rostrally and the nasal septum caudally. The maxillary process
incisive bone, including upper incisor teeth and the rostral up-
per lip, are derived from the primary palate. The nasal septum consists of bone, cartilage, and a patch
of soft tissue membrane that separates right & left halves of the nasal cavity.
Nasal and oral cavities communicate with one another following erosion of an oronasal
membrane that initially separated them. In mammals, nasal and oral cavities are again separated by
formation of a secondary palate that shifts the nasal-oral communication caudally into the pharynx.

fused nasal nasal

medial nasal septum bone
processes nasal
nasal
pit nasal
cavity
stomadeal cavity
cavity lateral
maxilla
nasal
process
maxillary
process oronasal
membrane oral tongue
mandibular oral tongue palatine mandible
cavity secondary
process cavity process palate

48
Palate:
Two palates are formed. The primary palate, which becomes incisive bone, is formed by
medial nasal processes. The secondary palate is formed by bilateral medial extensions of maxillary
processes. The extensions
(palatine processes) meet Palate Formation
at the midline, merg-
ing dorsally with nasal nasal pit nasal septum
septum and rostrally primary palate concha
with primary palate. The
nasal cavity
secondary palate (hard nasal cavity
palate) separates nasal nasal septum secondary
patate
and oral cavities. Caudal
extension of the second- secondary tongue
patate oral cavity
ary palate into the phar-
ynx, forms a soft palate Ventral Transverse
which divides the rostral View View
pharynx into dorsal (nasopharynx) and ventral (oropharynx) chambers.

• Cleft palate results from failure of the palate to close along the midline, leaving a gap
or cleft. The secondary palate is affected more commonly than the primary pal-
ate. The condition may be inherited or be the result of exposure to a teratogen (an
agent that causes birth defects). Cleft palate is often fatal in animals due to inabili-
ty to suckle or because of aspiration of milk into the lungs (aspiration pneumonia).
• Failure of medial nasal processes to fuse (primary cleft palate), produces hare lip
(cheiloschisis) and related defects. (Hare lip alone is normal is hares, sheep, etc.).

Conchae: Conchae (turbinates) are scrolls of thin bone covered by mucosa that grow into
each nasal cavity. Conchae originate as cartilaginous ridges of bones of the wall of the nasal cavity.
Paranasal sinuses: Sinuses arise as epithelial lined diverticula of the lining of the nasal cav-
ity. The extent of sinus development varies with species, most of the development occurs postnatally.
Newborn animals have cute, rounded heads that become angular with age as sinuses develop.
Vomeronasal organ: This is a specialized olfactory sense organ located rostrally in the floor
of each nasal cavity. The organ is produced by an outgrowth of nasal epithelium that forms a cau-
dally-closed tube.

Mouth:
The mouth (oral cavity) develops as a consequence of the formation of upper and lower jaws.
The first evidence of a mouth is the stomodeum, a rostral depression surrounded by prominences.
Outgrowth of the prominences produces a stomodeal cavity.
The deep wall of the stomodeum (oropharyngeal membrane) is composed of a layer of
surface ectoderm apposed to a layer of endoderm (rostral wall of the pharynx). The oropharyngeal
membrane soon becomes fenestrated and disappears (the palatoglossal fold marks its location in the adult).
Initially, stomodeal cavity and nasal pits are separated by an oronasal membrane. Subse-
quently, the oronasal membrane degenerates and oral and nasal cavities communicate freely. Eventu-
ally a secondary palate develops, shifting oral-nasal communication caudally into the pharynx.

49
 Lips and gingivae:
In the ectoderm lining the stomodeal cavity, an arc
oral cavity
of thickened ectoderm, the labiogingival lamina, forms (surface view)
along upper and lower jaws. The lamina invaginates into
underlying ectomesenchyme, forming a labiogingival dental lamina
groove. The groove forms the future vestibule. Tissue labiogingival lamina
external to the groove forms the future lips, and tissue TRANSVERSE
medial to the groove forms gingivae. Fusion of upper and VIEW

lower lips caudally forms cheeks.

LATERAL MEDIAL

Teeth:
An arc of periodically thickened ectoderm, situ- dental
ated inside of the labiogingival lamina, constitutes the labigingival bud
dental lamina. Invaginations of laminar cells form dental groove
buds. If a bud is to form a deciduous tooth, an additional
bud for its permanent replacement develops superficial
and medial to the deciduous dental bud. Each bud devel-
ops into a tooth in the following way: enamel
— the bud assumes a cup-shaped configuration organ
becoming an enamel organ. Condensation of ectomes- gingiva
enchyme within the concavity of the cup forms a dental lip
papilla;
-the concave epithelial layer of the enamel organ
induces ectomesenchyme of the dental papilla to form an permanent
epithelial layer of odontoblasts that deposit the dentin of tooth bud
the tooth;
dental
-the odontoblasts induce the concave epithelium papilla
of the enamel organ to differentiate into ameloblasts that
form enamel of the crown of the tooth; vestibule
-ectomesenchyme surrounding the enamel organ
condenses into a dental sac that gives rise to three layers:
1] Outer cells of the
dental sac differenti-
ate into osteoblasts
enamel
enamel that deposit bone of
the alveolus (socket ameloblast layer dentin
receiving the tooth). odontoblast layer tooth
CROWN pulp
2] Middle layer of
bone
the dental sac forms
periodontal ligament
(which anchors the tooth within the alveolus).
dentin
3] Inner cells of the sac become cementoblasts that produce cementum
(modified bone) which adheres to the surface of the tooth, particularly
the dentin surface of the root of the tooth.

pulp
cavity Note: Eventually, osteoclasts re-absorb encasing super-
ficial bone in preparation for tooth eruption.
ROOT
cementum

50
Tongue:
The tongue develops from four swellings situated on the floor of the pharynx:
-the body/apex of the tongue is formed by paired distal (lateral) swellings that fuse along the
midline and grow forward into the oral cavity, thereby acquiring an ectodermal coat. The body of
the tongue arises predominantly from the first pharyngeal arch. General sensation is from the trigeminal
nerve (V). The second pharyngeal arch also contributes. Taste sensation is from the facial nerve (VII).
-the root of the tongue is formed by the proximal swelling and covered by endoderm. It
arises from the third pharyngeal arch. Sensation is supplied by the glossopharyngeal nerve (IX) .
— the median swelling contributes significantly to the tongue only in ungulates (especially in
cattle where it forms a prominent bulge);
-muscles of the tongue originate from occipital somites (innervated by hypoglossal nerve (XII)).

median tongue
proximal swellings
distal
body of
tongue

I
I

II II

III III root

pharyngeal pharyngeal of
(branchial) IV pouches tongue
arches I-IV
I-IV larynx
IV
Canine Tongue
Dorsal View of Floor of Pharynx (roof removed) (dorsal view)

Salivary glands:
Salivary glands are derived from ectoderm (parotid, zygomatic, and labial and buccal accessory sali-
vary glands) or endoderm (mandibular and mono- and poly-stomatic sublingual salivary glands).

The process of salivary gland formation is typical of exocrine gland development in general:
— localized proliferation of surface epithelial cells forms a cellular cord that invades the
underlying ectomesenchyme; the initial site of proliferation ultimately becomes the duct opening
to the surface;
-the invading cord of cells begins to branch, ultimately becoming the main duct and
branched ducts of the gland;
-masses of epithelial cells accumulate at the ends of each branch, ultimately forming secre-
tory acini of the gland;
— the epithelial cords and masses canalize (become hollow) and the gland becomes func-
tional; growth of the jaw causes elongation of the main duct.
NOTE: A polystomatic gland is one that has many duct openings to the surface. Such glands arise as
a series of independent epithelial cords. Although they are independent glands, they appear to
form a single mass and in gross anatomy they are collectively identified as a single gland.
51
 Salivary Gland Adenohypophysis:
Formation
epithelium The adenohypophysis develops
brain
from an ectodermal thicken- ing (third ventricle)
(placode) in the roof of the
mesenchyme stomodeal cavity. The placode
epithelial cord evaginates to form an hypophy-
seal pouch (Rathke’s pouch).
The pouch separates from the
oral
surface ectoderm and wraps (stomadeal)
around the neurohypophysis, an cavity
outgrowth of the hypothalamus
epithelial cord (brain). Depending on species, the
branch cavity of the pouch may persist as a
cleft separating a pars tuberalis from neurohypophyseal
a more voluminous pars distalis of the bud
adenohypophysis.
hypophyseal
acinar (Rathke's)
cell mass NOTE: pouch
The hypophysis (pituitary gland)
consists of a neurohypophysis and an third
adenohypophysis. Both components ventricle
are controlled by the hypothalamus
of the brain. The neurohypophysis infundibulum
main duct is connected to the hypothalamus by
means of an infundibulum. Axons of
hypothalamic neurons run through neurohypophysis
the infundibulum and terminate in adenohypophysis
the neurohypophysis. Hypothalamic
acinus branch neurons must release hormones into the blood stream to control the
adenohypophysis.

Pharyngeal pouch derivatives:

A series of lateral evaginations of pharyngeal endoderm constitute pharyngeal pouches. There

are five pairs of pouches but in mammals the fifth pair is rudimentary, appearing as buds of the fourth.
The endoderm of each pharyngeal pouch is apposed to the ectoderm of a corresponding
pharyngeal cleft. Pharyngeal clefts separate adjacent pharyngeal arches. In fish, the apposed endoderm-ec-
toderm degenerates forming a branchial cleft that becomes a gill slit (in mammals only one branchial cleft develops and
it is transitory). [branchia (Gr.) = gills]

Pharyngeal pouches develop into various structures:

1st pouch —— tympanic (middle ear) cavity and auditory tube
2nd pouch --fossa for the palatine tonsil and the fold covering it
3rd pouch --external parathyroid gland and thymus
4th pouch --internal parathyroid gland
5th pouch —— parafollicular cells of thyroid gland (avian ultimobranchial body)

52
 I
I

II II

III III
Pharyngeal Pharyngeal
Arches IV Pouches
I-IV I-IV
IV

Floor of Pharynx (roof removed)

The thyroid gland develops from endoderm of the floor of the pharynx. Initially there is
formed a thyroid diverticulum connected to the pharynx by a thyroglossal duct. (The duct degener-
ates since the thyroid is an endocrine gland, but rarely a remnant of the duct persists as a cyst that can
enlarge and interfere with breathing by compressing the pharynx). Depending on the species, the thyroid
may remain single (pig) or split into bilateral lobes connected by an isthmus (horse) or become separate
paired lobes (dog).

Thyroid hormones have multiple metabolic effects. Parafollicular cells of the thyroid gland decrease blood
Ca++ while parathyroid gland hormones increases blood Ca++.

The thyroid and parathyroids are endocrine glands and thus they lack ducts to an epithelial
surface.

oral cavity

auditory
tube &
1
tympanic
cavity thyroid
gland
fossa of
palatine
2
tonsil
thymus &
3
parathyroid
(ext.)
4 & 5
parathyroid (int.) esophagus
& part of thyroid
Pharyngeal Pouch Derivatives
(ventral view)

53
 Development of the Nervous System
and Special Senses
Neurulation
The notochord induces overlaying ectoderm to become neuroectoderm and form a neural
tube. The following stages of neural tube formation are evident:
• neural plate-ectodermal cells overlaying the notochord become tall columnar, producing
a thickened neural plate (in contrast to surrounding ectoderm that produces epidermis of skin).
• neural groove-the neural plate is transformed into a neural groove.
• neural tube-the dorsal margins of the neural groove merge medially, forming a neural
tube composed of columnar neuroepithelial cells surrounding a neural cavity.
In the process of separating from overlaying ectoderm, some neural plate cells become de-
tached from the tube and collect bilateral to it, forming neural crest.

Note: • Neural tube becomes central nervous system (CNS), which consists of
the brain and spinal cord. The cavity of the tube (neural cavity) becomes
the ventricles of the brain and central canal of the spinal cord.
• Neural crest cells become those neurons of peripheral nervous system
(PNS) that have their cell bodies located in ganglia. They also become
neurolemmocytes (Schwann cells) of the PNS. Additionally, neural crest cells
become adrenal medulla cells, melanocytes of skin and a variety of structures in the face.

1 neural plate

2
ectoderm

notochord
neural
groove

neural
5 crest
neural
mergina l
crest neural cavity layer
mantle
4 neuroepithelium layer

54
 Central Nervous System
Formation of neurons and glial cells from neuroepithelium:
Neuroepithelium gives rise to neurons, glial cells (astrocytes Neural Tube
and oligodendrocytes), and ependymal cells (additionally, the CNS contains neural cavity
blood vessels and microglial cells derived from mesoderm).
neuroepithelium
Neuroepithelial cells have processes which contact the inner and outer
surfaces of the neural tube; they undergo mitotic division in the following manner:
-the nucleus (and perikaryon) moves away from the neural cavity for wall
interphase (DNA synthesis);
-the nucleus moves toward the neural cavity and the cell becomes
spherical and looses its connection to the outer surface of the neural tube for mito-
sis; this inward-outward nuclear movement is repeated at each cell division.

outside wall
lumen side
Some cell divisions are differential, producing neuroblasts
which give rise to neurons or glioblasts (spongioblasts) which give
rise to glial cells (oligodendrogliocytes and astrocytes). Neuroblasts and
glioblasts lose contact with surfaces of the neural tube and migrate
toward the center of the neural tubewall.
Note: Microglial are derived from mesoderm associated with
invading blood vessels.

Layers and plates of the neural tube: mitosis

Accumulated neuroblasts and glioblasts form the mantle
interphase
layer, a zone of high cell density in the wall of the nerual tube. Cells
that remain lining the neural cavity are designated ependymal cells;
they form an ependymal layer. Surrounding the mantle layer, a cell-
sparse zone where axons of neurons and some glial cells are present
is designated the marginal layer. The mantle layer becomes gray mat-
ter and the marginal layer becomes white matter of the CNS.

central canal
neuroepithelium neural cavity ependymal layer
mantle layer gray matter
marginal layer white matter
Neural Tube Embryonic Spinal Cord
The lateral wall of the neural tube is divided roof plate
into two regions ( plates). A bilateral indentation evi-
alar
dent in the neural cavity (the sulcus limitans) serves
as a landmark to dplate
ivide each lateral wall into an alar
plate (dorsal) and a basal plate (ventral). Midline re- sulcus
gions dorsal and ventral to the neural cavity constitute, limitans
respectively, the roof plate and the floor plate.
The basal plate contains efferent neu- basal plate
floor plate
rons that send axons into the PNS.
Embryonic Cord Regions
The alar plate contains neurons that
receive input from the PNS.
55
 Generally, neurons are incapable of cell division (however, a few neurons do di-
vide, e.g., neurons in olfactory epithelium). The last division of a neuroblast results in
two neurons that are able to migrate but unable to divide.
Note: • A typical neuron has a cell body (perikaryon) and numerous processes emanating from the cell
body. One process, the axon, is generally long and often encased in a myelin sheath formed by
glial cells. Unstained myelin has a white “color”.
• White matter refers to CNS regions that have a high density of myelinated axons. Gray matter
has sparse myelinated axons and generally a high density of neuron cell bodies.

Formation of the telencephalon

(cerebrum)
Central Nervous System
The cranial end of the neural forebrain
tube forms three vesicles (enlarge-
ments) that further divide into the diencephalon
five primary divisions of the brain. optic cup
Caudal to the brain the neural tube
midbrain mesencephalon
develops into spinal cord.
(midbrain)
Flexures: During development, the
brain undergoes three flexures which gener- hindbrain
ally disappear (straighten out) in domestic metencephalon
animals.
The midbrain flexure occurs at the
level of the midbrain. myelencephalon
The cervical flexure appears at the spinal cord (medulla oblongata)
junction between the brain and spinal cord
(it persists slightly in domestic animals).
The pontine flexure is concave
dorsally (the other flexures are concave spinal cord
ventrally). Brain Vesicles
Brain Divisions

Adult CNS Structures Derived From Embyonic Brain Divisions

Embryonic Derived Definitive Associated
Brain Division BrainStructures BrainCavities Cranial Nerves

FOREBRAIN
Telencephalon Cerebrum Lateral ventricles Olfactory (I)

Diencephalon Thalamus; Third Ventricle Optic (II)

hypothalamus; etc.

MIDBRAIN
Mesencephalon Midbrain Mesencephalic aqueduct III & IV

HINDBRAIN
Metencephalon Pons and Cerebellum V
Fourth ventricle
Myelencephalon Medulla Oblongata VI—XII

Note: The portion of brain remaining after the cerebrum and cerebellum are removed is referred to as the brain stem.
56
Spinal cord development
-the neural cavity becomes central canal
lined by ependymal cells; central canal
ependymal layer
-growth of alar and basal plates, but not r oof
and floor plates, results in symmetrical right and left gray matter
halves separated by a ventral median fissure and a white matter
dorsal median fissure (or septum); Embryonic Spinal Cord
-the mantle layer develops into gray matt er,
i.e., dorsal and ventral gray columns separated by intermediate gray matter (in profile, the columns are usually called
horns); cell migration from the basal plate produces a lateral gray column (horn) at thoracic and cranial lumbar levels of
the spinal cord (sympathetic preganglionic neurons);
-the marginal layer becomes white matter (which is subdivided bilaterally into a dorsal funiculus
(bundle), a lateral funiculus, and a ventral funiculus ).

Enlargements of spinal cord segments that innervate limbs (cervical and lumbo-
sacral enlargements) are the result of greater numbers of neurons in those segments,
due to less neuronal degeneration compared to segments that do not innervate limbs.

Hindbrain: Medulla oblongata and pons

-alar plates move laterally and the cavity of the neural tube expands dorsally forming a
fourth ventricle; the roof of the fourth ventricle (roof plate)
is stretched and reduced to a layer of ependymal cells covered ependymal
by pia mater; a choroid plexus develops bilaterally in the roof cell layer pia mater
choroid plexus
of the ventricle and secretes cerebrospinal fluid;
-the basal plate (containing efferent neu-
rons of cranial nerves) is positioned medial to the alar plate
alar plate and ventral to the fourth ventricle; mantle layer
-white and gray matter (marginal & mantle marginal layer
basal plate
layers) become intermixed (unlike spinal cord);
cerebellar development adds extra structures. Medulla Oblongata

Hindbrain: Cerebellum
NOTE: • Adult cerebellum features surface gray matter, called cerebellar cortex, and three pair of
cerebellar nuclei located deep within the cerebellar white matter. The cerebellum connects to
the brain stem by means of three pair of cerebellar peduncles, each composed of white matter
fibers.
• Cerebellar cortex is composed of three layers: a superficial molecular layer which is rela-
tively acellular; a middle piriform (Purkinje) cell layer consisting of a row of large cell bodies;
and a deep granular (granule cell) layer composed of numerous very small neurons.
• The cerebellum functions to adjust muscle tone and coordinate posture and movement so
they are smooth and fluid vs. jerky and disunited.

-bilateral rhombic lips are the first evidence of cerebellar development; the lips are expan-
sions of the alar plate into the roof plate; the rhombic lips merge medially, forming a midline isthmus (the lips
form the two cerebellar hemispheres and the isthmus forms the vermis of the cerebellum);
57
 midbrain
— cellular migrations: flexure
• superficial and deep layers of neu-
midbrain cerebrum
rons are evident within the mantle layer of the future
cerebellum; the deep cells migrate (pass the superfi- cerebellum
cial cells) toward the cerebellar surface and become
Purkinje cells of the cerebellar cortex; meanwhile, cervical
flexure diencephalon
neurons of the superficial layer migrate deeply and pons neurohypophysis
become cerebellar nuclei; medulla oblongata
• neuroblasts located laterally in the Brain Divisions & Flexures
rhombic lip migrate along the outer surface of the
cerebellum, forming an external germinal layer (which continues to undergo mitosis); subsequently,
neurons migrate deep to the Purkinje cells and form the granule cell layer of the cerebellar cortex;
• some alar plate neurons migrate to the ventral surface of the pons, forming pontine nuclei which send
axons to the cerebellum.

Migration of neuron populations past one another allows connections to be estab-

lished between neurons of the respective populations. Neurons that fail to connect are
destined to degenerate. Connections are made by axons that subsequently elongate as
neurons migrate during growth.

Midbrain
-the neural cavity of the midbrain becomes mesencephalic aqueduct (which is not a ventricle
because it is completely surrounded by brain tissue and thus it lacks a choroid plexus).
-alar plates form two pairs of dorsal bulges which be- Midbrain
come rostral and caudal colliculi (associated with visual and auditory
reflexes, respectively); colliculus
mesencephalic
-the basal plate gives rise to oculomotor (III) and troch- aqueduct
lear (IV) nerves which innervate muscles that move the eyes.

Note: The midbrain is the rostral extent of the basal plate (efferent
neurons).

Forebrain (derived entirely from alar plate)

future choroid plexus
Diencephalon: mantle layer cerebral cortex
-the neural cavity expands
dorsoventrally and becomes the
narrow third ventricle, the roof plate lateral lateral
ventricle third ventricle
is stretched and choroid plexuses develop
bilaterally in the roof of the third ventricle ventricle
and secrete cerebrospinal fluid;

— the floor of the third basal

nucleus
ventricle gives rise to the neurohyp- diencephalon
ophysis (neural lobe of the pituitary telencphalon (cerebrum)
gland);
Developing Forebrain (transverse section)

58
 -the mantle layer of the diencephalon gives rise to thalamus, hypothalamus, etc.; the thal-
amus enlarges to the point where right and left sides meet at the midline and obliterate the center of the third ventricle.
-the optic nerve develops from an outgrowth of the wall of the diencephalon.

laminal terminalis cerebral hemisphere

cerebral
interventricular cortex
foramen
lateral basal
ventricle
lateral nucleus
ventricle
basal
third nucleus third
ventricle ventricle
optic cup

diencephalon Telencephalon (cross section)

surrounding diencephalon
Forebrain (dorsal view)

Telencephalon (cerebrum):

-bilateral hollow outgrowths become right and left cerebral hemispheres; the cavity of each
outgrowth forms a lateral ventricle that communicates with the third ventricle via an interventricular
foramen (in the wall of each lateral ventricle, a choroid plexus develops that is continuous with a choroid plexus of the
third ventricle via an interventricular foramen);
-at the midline, the rostral end of the telencephalon forms the rostral wall of the third ven-
tricle (the wall is designated lamina terminalis);
-the mantle layer surrounding the lateral ventricle in each hemisphere gives rise to basal
nuclei and cerebral cortex;
-cellular migrations that form cerebral cortex:
• from the mantle layer, cells migrate radially to the surface of the cerebral hemi-
sphere, guided by glial cells that extend from the ventricular surface to the outer surface of the cere-
bral wall (thus each locus of mantle gives rise to a specific area of cerebral cortex);
• migration occurs in waves; the first wave (which becomes the deepest layer of
cortex) migrates to the surface of the cortex; the second wave (which forms the next deepest layer of
cortex) migrates to the cortical surface, passing through first wave neurons which are displaced to a
deeper position; the third wave . . . etc. (the cerebral cortex has six layers.

Cell connections are established within the cerebral cortex as waves of newly
arriving neurons migrate through populations of neurons that arrived earlier.

NOTE: Carnivores are born with a nervous system that does not mature until about six weeks
postnatally (mature behavior is correspondingly delayed). In herbivores, the nervous
system is close to being mature at birth.

59
 Peripheral Nervous System
NOTE: • The peripheral nervous system (PNS) consists of cranial and spinal nerves. Nerve fibers
within peripheral nerves may be classified as afferent (sensory) or efferent (motor) and
as somatic (innervating skin and skeletal muscle) or visceral (innervating vessels and
viscera). The visceral efferent (autonomic) pathway involves two neurons: 1] a pregan-
glionic neuron that originates in the CNS and 2] a postganglionic neuron located entirely
in the PNS. The glial cell of the PNS is the neurolemmocyte (Schwann cell).
• All afferent neurons are unipolar and have their cell bodies in sensory ganglia, either
spinal ganglia on dorsal roots or ganglia associated with cranial nerves. Somatic efferent
and preganglionic visceral efferent neurons have their cell bodies located in the CNS, but
their axons extend into the PNS. Postganglionic visceral efferent neurons have their cell
bodies in autonomic ganglia.

-neurolemmocytes (Schwann cells) arise from neural crest and migrate throughout the
PNS, ensheathing and myelinating axons and forming satellite cells in ganglia;

-afferent neurons originate

from neural crest as bipolar cells
that subsequently become unipolar; spinal ganglion
in the case of cranial nerves, af-
ferent neurons also originate from neural tube
placodes (placode = localized thickening lemmocytes
ventral root
of ectoderm in the head); (around axons)
notochord
autonomic
-postganglionic visceral ganglion
efferent neurons arise from neural aorta
adrenal
crest, the cells migrate to form au- medulla
tonomic ganglia at positions within
the head, or beside vertebrae (along autonomic
dorsal
sympathetic trunk), or near the mesentery
ganglion
aorta, or in the gut wall (the latter are melanocytes
parasympathetic and come from sacral and enteric
gut autonomic
hindbrain regions);
ganglion

-somatic efferent neurons Developing Peripheral Nervous System

and preganglionic visceral efferent
neurons arise from the basal plate
of the neural tube; their cell bodies remain in the CNS and their axons join peripheral nerves;

Peripheral nerves establish contact early with the nearest somite, somitomere,
placode, or branchial arch and innervate derivatives of these embryonic structures.

Innervation continuity is retained even when the derivatives are considerably displaced
or when other structures have obstructed the pathway. The early establishment of an innervation
connection explains why some nerves travel extended distances and make detours to reach distant
inaccessible targets. The foremost example is the recurrent laryngeal nerve which courses from the brainstem to the
larynx via the thorax, because the heart migrates from the neck to the thorax pulling the nerve with it.

60
 Note: Cranial nerves innervate specific branchial arches and their derivatives:
trigeminal (V) - innervates first branchial arch (muscles of mastication)
facial (VII) - innervates second branchial arch (muscles of facial expression)
glossopharyngeal (IX) - innervates third branchial arch (pharyngeal muscles)
vagus (X) - 4 & 6 branchial arches (muscles of pharynx, larynx, & esophagus)

Formation of Meninges

Meninges surround the CNS and the roots of spinal and cranial nerves.

Three meningeal layers (dura mater, arachnoid, and pia mater) are formed as follows:
-mesenchyme surrounding the neural tube aggregates into two layers;
-the outer layer forms dura mater;
-cavities develop and coalesce within the inner layer, dividing it into arachnoid and pia
mater; the cavity becomes the subarachnoid space which contains cerebrospinal fluid.

61
 Special Senses
Formation of the Eye
Both eyes are derived from a single field of the neural plate. The single field separates into
bilateral fields associated with the diencephalon. The following events produce each eye:
-a lateral diverticulum from the diencephalon forms an optic vesicle attached to the dien-
cephalon by an optic stalk;
-a lens placode develops in the surface ectoderm where it is contacted by the optic vesicle;
the lens placode induces the optic vesicle to invaginate and form an optic cup while the placode
invaginates to form a lens vesicle that invades the concavity of the optic cup;
-an optic fissure is formed by invagination of the ventral surface of the optic cup and optic
stalk, and a hyaloid artery invades the fissure to reach the lens vesicle;

optic
cup
optic
stalk lens
vesicle

NOTE: The optic cup forms the retina and contributes to formation of the ciliary
body and iris. The outer wall of the cup forms the outer pigmented layer
of the retina, and the inner wall forms neural layers of the retina.
• The optic stalk becomes the optic nerve as it fills with axons traveling
from the retina to the brain.
• The lens vesicle develops into the lens, consisting of layers of lens
fibers enclosed within an elastic capsule.
• The vitreous compartment develops from the concavity of the optic
cup, and the vitreous body is formed from ectomesenchyme that enters the
compartment through the optic fissure.

Optic Stalk Optic Nerve

central
vessels
(in primates)

hyaloid artery axons from the retina

optic nerve fibers
in optic fissure

62
 -ectomesenchyme (from neural crest) surrounding the optic cup condenses to form inner
and outer layers, the future choroid and sclera, respectively;
-the ciliary body is formed by thickening of choroid ectomesenchyme plus two layers of
epithelium derived from the underlying optic cup; the ectomesenchyme forms ciliary muscle and the collage-
nous zonular fibers that connect the ciliary body to the lens;
-the iris is formed by cho-
roid ectomesenchyme plus the super-
ficial edge of the optic cup; the outer Anterior Eyeball and Eyelids
layer of the cup forms dilator and lacrimal
dorsal conjunctival
gland
constrictor muscles and the inner layer eyelid sac optic cup
forms pigmented epithelium; the ecto- cornea
mesenchyme of the iris forms a pupil- vitreous
lary membrane that conveys an ante- compartment
rior blood supply to the developing
lens; when the membrane degenerates
following development of the lens, a
pupil is formed; hyaloid
lens artery
-the cornea develops from two
sources: the layer of ectomesen-
chyme that forms sclera is induced by
the lens to become inner epithelium
and stroma of the cornea, while sur- ciliary
face ectoderm forms the outer epithe- body
anterior
lium of the cornea; the anterior cham-
compartment
ber of the eye develops as a cleft in
pupillary
the ectomesenchyme situated between iris
membrane
the cornea and the lens;
-the eyelids are formed by upper and lower folds of ectoderm, each fold includes a mesen-
chyme core; the folds adhere to one another but they ultimately separate either prenatally (ungulates)
or approximately two weeks postnatally (carnivores); ectoderm lining the inner surfaces of the folds
becomes conjunctiva, and lacrimal glands develop by budding of conjunctival ectoderm;
-skeletal muscles that move the eye (extraocular eye mm.) are derived from rostral somito-
meres (innervated by cranial nerves III, IV, and VI).

Clinical considerations:
• The ungulate retina is mature at birth, but the carnivore retina does not fully mature until about 5
weeks postnatally.
• Retinal detachment occurs between the neural and outer pigmented layers of the retina (inner
and outer walls of the optic cup) which do not fuse but are held apposed by pressure of the vitre-
ous body.
• Coloboma is a defect due to failure of the optic fissure to close.
• Microphthalmia (small eye) results from failure of the vitreous body to exert sufficient pressure
for growth, often because a coloboma allowed vitreous material to escape.
• Persistent pupillary membrane results when the pupillary membrane fails to degenerate and
produce a pupil.

63
Formation of the Ear
The ear has three components: external ear, middle ear, and inner ear. The inner ear contains
sense organs for hearing (cochlea) and detecting head acceleration (vestibular apparatus), the latter
is important in balance. Innervation is from the cochlear and vestibular divisions of the VIII cranial nerve. The
middle ear contains bones (ossicles) that convey vibrations from the tympanic membrane (ear drum)
to the inner ear. The outer ear channels sound waves to the tympanic membrane.
BRAIN
vestibulocochlear
nerve

ossciles
(bones)
inner
ear outer
ear

tympanic
cochlea membrane

middle
ear EAR
auditory tube (to nasopharynx) (in section)
Inner ear:
-an otic placode develops in surface ectoderm adjacent to the hindbrain; the placode in-
vaginates to form a cup which then closes and separates from the ectoderm, forming an otic vesicle
(otocyst); an otic capsule, composed of cartilage, surrounds the otocyst;
-some cells of the placode and vesicle become neuroblasts and form afferent neurons of the vestibulocochlear
nerve (VIII);
-the otic vesicle undergoes differential growth to form the cochlear duct and semicircular
ducts of the membranous labyrinth; some cells of the labyrinth become specialized receptor cells found in macu-
lae and ampullae;
-the cartilagenous otic capsule undergoes similar differential growth to form the osseous
labyrinth within the future petrous part of the temporal bone.

Inner Ear vestibular apparatus

Development

otic
vesicle

64
cochlea
Middle ear:
-the dorsal part of the first pharyngeal pouch
forms the lining of the auditory tube and tympanic cavity HIND
(in the horse a dilation of the auditory tube develops into the guttural BRAIN
pouch);
-the malleus and incus develop as endochondral otic
bones from ectomesenchyme in the first branchial arch and vesicle
the stapes develops similarly from the second arch (in fish,
these three bones have different names; they are larger and function as external
jaw bones). auditory
meatus
Outer ear: pharynx tympanic
-the tympanic membrane is formed by apposition of membrane
endoderm and ectoderm where the first pharyngeal pouch is auditory tube middle ear
apposed to the groove between the first and second pha-
ryngeal (branchial) arches; Auditory Tube Formation
— the external ear canal (meatus) is formed by the groove between the first and second bran-
chial arches; the arches expand laterally to form the wall of the canal and the auricle (pinna) of the
external ear.

Taste buds
Taste buds are groups of specialized (chemoreceptive) epithelial cells localized principally on
papillae of the tongue. Afferent innervation is necessary to induce taste bud formation and maintain
taste buds. Cranial nerves VII (rostral two-thirds of tongue) and IX (caudal third of tongue) innervate the taste buds of
the tongue.

Olfaction
Olfaction (smell) involves olfactory mucosa located caudally in the nasal cavity and the
vomeronasal organ located rostrally on the floor of the nasal cavity. Olfactory neurons are chemore-
ceptive; their axons form olfactory nerves (I).
-an olfactory (nasal) placode appears bilaterally as an ectodermal thickening at the rostral
end of the future upper jaw; the placode invaginates to form a nasal pit that develops into a nasal
cavity as the surrounding tissue grows outward; in the caudal part of the cavity, some epithelial cells
differentiate into olfactory neurons;
-the vomeronasal organ develops as an outgrowth of nasal epithelium that forms a blind
tube; some epithelial cells of the tube differentiate into chemoreceptive neurons.

65
 Appendix I
Gametogenesis
Germ cells provide the continuity of life between generations of a species, by passing on
chromosomal DNA which contains developmental information for the species. Diploid (2N) germ
cells are capable of producing haploid (lN) gametes. Fusion of haploid gametes produces a diploid
zygote (the beginning of a new individual of the species).
Note: N = the number of pairs of chromosomes, i.e., the number of chromosomes each parent contributes to the
new individual.

germ cells

Life
adult Cycle zygote

embryo

Gametogenesis . . .
refers to the formation of haploid (lN) gametes (sperm or oocytes) by diploid (2N) germ
cells (primary spermatocytes or primary oocytes) through a process called meiosis.

Spermatogenesis (duration varies: 34 days in mouse; 36 days in stallion; 74 days in human)

• spermatocytogenesis
-spermatogonia (2N) proliferate, producing themselves & primary spermatocytes (2N)
-primary spermatocyte (2N) produces two secondary spermatocytes (lN) via Meiosis I
-two secondary spermatocytes (lN) divide into four spermatids (lN) via Meiosis II
• spermiogenesis
-transformation of a spermatid into a sperm (spermatozoon) cell (duration l8 days)

Oogenesis (duration: from before birth to some time between puberty and loss of fertility)
-oogonia (2N) proliferate themselves and primary oocytes (2N) in the embryo & fetus
- primary oocyte (2N) remains in prophase of Meiosis I until it is ovulated;
then, it divides into a secondary oocyte (lN) and a polar body (lN)
- following fusion with sperm , the secondary oocyte (lN) completes Meiosis II;
the result is a fertilized ovum or zygote (now 2N)

NOTE: Following Meiosis I, all of the oocyte cytoplasm becomes associated with just one of the
daughter cells, called a secondary oocyte. The other daughter cell (nucleus) is called a polar body.
Following Meiosis II, all of the oocyte cytoplasm becomes associated with just one of the daugh-
ter cells, called an ovum. The other daughter cell (nucleus) is called a polar body. Since the first
polar body also undergoes Meiosis II, a total of three polar bodies are produced by meiosis.

66
 Gametogenesis
Spermatogenesis (formation of spermatozoa)
A] Spermatocytogenesis (formation of spermatids in seminiferous tubules)
primordial spermatogonia (2N)
germ cells mitosis (throughout post-puberty)
(germ stem cells) incomplete cell division(cytoplasmic bridges)

primary spermatocyte (2N)

Meiosis I

two secondary spermatocytes (N)

Meiosis II

four spermatids (each N)

B] Spermiogenesis (transformation of spermatids to spermazoa)
— elongate nucleus, loss of cytoplasm & cytoplasmic bridges, formation of acrosome & tail
— transformation occurs while linked to a Sertoli cell
— spermatozoa are release into lumen of seminiferous tubule

Oogenesis (formation of an ovum)

primordial oogonia (2N)
germ cells mitosis (occurs only in an embryo)

primary oocytes (2N) in prophase of meiosis I

(oocyte in primordial follicle,
surrounded by flat follicular cells)
birth (oocyte in primary follicle,
surrounded by cuboidal follicular cells)
puberty (oocyte in secondary & tertiary follicles,
(selected follicles/estrus) surrounded by zona pellucida, layers
of follicular cells, and fluid chamber)

ovulation prophase, etc. of Meiosis I completed

spermatozoan (N) secondary oocyte (N) + first polar body

(NOTE: horse & dog sperm unite with
a primary vs a secondary oocyte) Meiosis II completed

fertilized ovum (2N zygote) + second polar body

Note: Fertilization begins with union of male and female gametes
and ends with the start of zygote cell division (cleavage). 67
 Appendix II
Mitosis and Meiosis

Somatic Cell Cycle and Cell Division (Mitosis):

(two chromatids/chromosome)
interphase

Somatic
interphase
(synthesis) Cell mitosis
Cycle

interphase
(one chromatid/chromosome)

Interphase:
period prior to DNA synthesis [G1 = days or G0 = very long time];
period of DNA synthesis [S = 10 hrs.];
period of preparation for mitosis [G2 = 1 hr].

Synthesis = each double-stranded helix of DNA (one chromatid/chromosome) becomes

two double-stranded helicies of DNA (two chromatids/chromosome).

Mitosis = cell division where each of two daughter cells receives chromosomal
material identical to the parent cell (i.e., one of two chromatids per chromosome).
Stages of mitosis:
Prophase — chromosomes become visible and the nuclear membrane disappears
under the light microscope (90 min.) ;
Metaphase — individual, double-chromatid chromosomes align randomly at the equatorial
region between centrioles (30 min.) ;
Anaphase — the two chromatids per chromosome separate as the centromere divides and
each chromatid becomes a chromosome in a new nucleus (5 min.) ;
Telophase — chromosomes become invisible and the nuclear membrane reappears

68
 Diploid Somatic Cell

chromosomes
are uncoiled from
telophase
Dad
& of a
DNA preceding
synthesis is from mitotic
taking place Mom
division
nucleus
cytoplasm

Interphase

Mitosis

2 chromatids
individual
per
chromosomes
chromosome
align at
linked by a
equator
centromere

Prophase Metaphase

Two identical daughter cells (diploid)

individual
chromatids
separate
& each goes
to a daughter
cell

Telophase Anaphase

69
Germ cell division: (two chromatids/chromosome)
A diploid germ cell diploid germ cell
gamete
initially undergoes Meiosis I,
a reduction division: [2N —> (sperm or ovum)
2(1N)]. haploid with one Germ
chromatid/chromosome
Then each of two haploid Cell
daughter cells undergoes Meiosis meiosis I I meiosis I
II, a mitotic-like division.
Cycle
Four gametes (four sper-
haploid germ cell
matids or one ovum plus three (two chromatids/chromosome)
polar bodies) are produced.

Meiosis: (!ollowing interphase in which DNA synthesis occurs)

Meiosis I (reduction division: one diploid —> two haploid cells)
Prophase
— chromosomes become visible (as paired chromatids joined at centromeres)
— homologous chromosomes are paired (linked by a synaptonemal complex)
Note: chromatids of linked homologous chromosomes may exchange comparable DNA,
i.e., exchange genes (genetic cross-over)
Metaphase
— homologous chromosome pairs align at equatorial region between centrioles
Anaphase
— homologous chromosome pairs separate (one chromosome of a pair
moves toward one centriole and the other toward the other centriole).
Note: haploid daughter cells inherit different assortments of maternal/paternal chromosomes.
The number of possible assortments = 2N, where N = number of chromosomes/gamete,
e.g., for human 223 = over 8 million. Including cross-overs = incalculable variety.
Telophase
— chromosomes become less visible; nuclear membrane reappears; cytoplasm divi-
sion occurs.
Crossover during Meiosis I
Meiosis II (mitosis-like division of each haploid cell) Homolgous Chromosome Pair
Prophase
— chromosomes visible (very brief pe-
riod) paternal maternal
chromatids chromatids
Metaphase
— individual chromosomes align at equatorial
region between centrioles.
Anaphase centromere

— the two chromatids per chromosome

separate at the centromere region
— each chromatid moves toward its maternal/paternal
respective centriole and becomes a chromosome in a genetic exchange
new nucleus synaptonemal
Telophase complex
— chromosomes become less visible;
nuclear membrane reappears; cytoplasm division occurs (cytokinesis).

70
 Primary spematocyte or oocyte (diploid germ cell)

chromosomes
are uncoiled from
telophase
Dad
& of a
DNA preceding
synthesis is from mitotic
taking place Mom division
nucleus
cytoplasm

Interphase

Meiosis I

2 chromatids
per
homologous
chromosome
chromosome
&
pairs
homologous
align at
chromosomes equator
linked
together

Prophase Metaphase

Secondary spermatocytes or oocytes (haploid)

homologous
pairs separate
& either
homologus
1N 2N chromosome
goes to a
daughter cell

Telophase Anaphase

Meiosis II Prophase Metaphase Anaphase Telophase

Prophase
Metaphase
Anaphase
Telophase

Gametes
(sperm or ova) Gametes 71
(sperm or ova)
 Appendix III
Congenital Anomalies of Clinical Significance
(See also Noden and De Lahunta, Embryology of Domestic Animals)

This is a small representation of the many anomalies which can occur. It is presented here to
stimulate an awareness in practitioners-to-be to that congenital malformations are etiological factors
to be considered in making differential diagnoses

A. Placentation:

1. Hydrops of the amnion or allantois.

Accumulation if excessive fluid in either amniotic or allantoic cavities results in fetal death.
If not relieved, in late pregnancy they can cause uterine or prepubic tendon rupture. Progressive
bilateral abdominal distention, anorexia, and recumbency are signs of their occurrence.

2. Strangulation by umbilical cord.

In species with long umbilical cords, e.g., swine, neck or limb strangulation in varying degree
may occur.

B. Face, mouth, nasal cavity, and pharynx.

1. Cheiloschesis (cleft lip), palatoschisis (cleft palate).

Cleft lip is caused by failure of fusion of medial nasal and maxillary processes; cleft palate is
caused by failure of medial palatine processes to fuse.

2. Branchial cyst (no opening), branchial sinus (opening to exterior), branchial fistula
(openings to interior and exterior).
These result from failure of involution of the branchial apparatus caudal to branchial arch II.
Cysts and sinuses are minor problems, and can be surgically relieved.

3. Heterotopic polyodontia (dentigerous cyst, "ear teeth").

Primordia of enamel organs escape to the exterior and develop tooth structures anchored on
the parietal bone or base of the ear. These cause festering problems and must be relieved surgically.

4. Thyroglossal duct cyst.

Failure of involution of thyroglossal duct is the cause. A surgically removable fluid-filled
cyst seen at birth interferes with breathing.

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C. Digestive tract.

1. Meckel’s diverticulum.
Persistence, inflammation, and rupture of this structure, which is an appendix-like remnant
of the yolk stalk, results in colic, with peritonitis.

2. Atresia of the jejunum, ileum, colon, rectum.

A lack of epithelial canalization and gut wall development results in feed impaction and
death if surgical intervention cannot be made. Some evidence suggests that one cause is manual
manipulataion of fetal membranes rectally in pregnancy diagnosis.

3. Imperforate anus.
This results from lack of involution of the cloacal membrane, and leads to fatal feed impac-
tion. Where anal musculature is developed, surgical removal of the cloacal membrane offers tempo-
rary if not permanent relief.

D. Lower respiratory tract.

1. Tracheoesophageal fistula.
This results from a partial persistence of the laryngotracheal groove. Its presence in the
newborn causes refluxing of feed through the upper respiratory tract, and inhalation pneumonia.
Surgical treatment is difficult.

2. Barker foal syndrome: hyalin disease.

This is believed to result from a lack of production of pulmonary surfactant, which may be
temporary. Gasping of the newborn is a sign of its presence.

E Heart and arterial system.

1. Ectopia cordis.
Here the heart remains in the cervical region where it was formed embryologically. Though
some animals survive to adulthood, they become unthrifty.

2. Intertrial septal defect (ASD); interventricular septal defect (VSD).

An unthrifty animal usually results.

3. Tetrology of Fallot.
Three primary abnormalities are: ventricular septal defect; shift of left ventricular outflow to
the right; and pulmonary stenosis.
A resulting fourth abnormality is a hypertrophy of the right ventricle.

4. Persistent truncus arteriosus.

This is due to a partial or complete lack of formation and fusion of truncus spiral ridges. De-
pending upon the severity of malformation, cyanosis and fatigue, poor growth, and death may occur.

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 5. Persistent ductus arteriosus.
Failure of closure at birth results in the so-called blue baby condition, wherein poorly oxy-
genated blood is delivered to the whole body except the head, neck, and right fore appendage re-
gions.

6. Right aortic arch.

The left aortic arch normally forms the ascending aorta; an anomalous right arch, together
with the normal left ductus arteriosus (ligamentum arteriosum), forms a strangualting vascular ring
around the esophagus and trachea. Inability to swallow solid feed in young animals is a first symp-
tom.

7. Ectopic right subclavian artery.

Origin of the right subclavian artery from the ascending aorta instead of the brachiocaphalic
trunk also results in a strangulation of the esophagus and trachea.

8. Persistent vitelloumbilical band.

Especially in equidae where there is a well developed yolk sac, the left vitelline artery and
yolk stalk may persist, forming a band between the ileum and umbilicus. Intestinal strangulation
may result. Development of colic is a first symptom.

F. Venous and lymphatic systems.

1. Portosystemic shunts.
Venous return from the gut should first pass through the liver since it contains toxic sub-
stances normally metabolized in the liver. One anomaly which prevents this return is an anomalous
persisting ductus venosus. The other is a central or peripheral portal-venous shunt to the caudal
vena cava or azygous vein. Both result in young animals showing abnormal nervous behavior as a
first symptom.

2. Congenital hereditary lymphoedema.

Absence of lymph vascular connections to the venous system result in edema of the involved
body regions.

G. Body cavities.

1. Pleuroperitoneal hernia.
Failure of closure of one or both pleuroperitoneal folds results in intestinal herniation into the
pleural cavity. Labored breathing is a symptom.

2.Peritoneopericardial diaphragmatic hernia.

During fetal development the liver dissects away from the transverse septum, occasionally
leaving a central weakness in the fibrous part of the diaphragm. Intestinal herniation through this
area into the pericardial sac will result in abnormal cardiac sounds and dyspnoea.

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H. Urinary and genital systems.

Three facts render the urogenital system vulnerable to anomalies, as follows: 1), they arise
in part by by faulty division of the cloaca;into rectum and urogenital sinus; 2), in both sexes, espe-
cially the male, part of the urinary tract is co-opted during fetal development for use in the forma-
tion of the internal genital system; and 3), there is a marked translocation of urinary and reproduc-
tive duct terminals during fetal development.

1. Ectopic ureter.
Entry of the ureters into the vagina or urethra results in dribbling of urine and bladder infec-
tion. Hydronephrosis may also result due to blockage of terminal ureteral orifices.

2. Urorectal fistula: rectovesicular, rectovestibular, rectourethral.

Due to faulty separation of the cloaca into rectum and urogenital sinus a fistulous tract may
remain. This leads to abnormal elimination of urine and feces, and urinary tract infection.

3. Patent urachus.
The urachus is the urinary canal of the fetus. It becomes the median ligament of the bladder.
Moistness or dribbling of urine at the umbilicus following birth results if it remains patent.

4. Double cervix.
This results from lack of fusion of the paramesonephric ducts beyond the body of the uterus.
It may present parturition difficulties.

5 Paramesonephric duct atresia (White heifer disease).

This consists of the absence of the paramesonephric duct derived parts of the female tract
(oviducts, uterus, cervix, and vagina). Ovaries are normal. The cause is known; it is not limited to
white cattle.

6. Hypospadia.
Failure of urethral folds to fuse results in an opening of the urethra on the ventral surface of
the penis

I. Nervous system.

Aganglionosis.
This results from lack of migration of neural crest cells to form intestinal ganglia. This con-
dition, seen especially in Overo spotted horses, results in a flaccid, atonic large intestine. It is fatal
for newborn animals due to intestinal impaction.

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J. Musculoskeletal system.

1. Premature physeal closure (achondroplasia, chondrodysplasia).

This may be a generalized anomaly of the appendages, or involve one of the long bones. In
the latter instance, normal appendage use can be restored through orthopedic surgery. The cause is
unknown.

2. Spina bifida.
This results from a failure of the vertebral arch to form dorsally over the vertebral canal. It
usually occurs in the lumbar and sacral regions, and may interfere with locomotion.

3. Flexural and angular limb deformities (arthrogryposis).

These occur most frequently in equidae. Preliminary investigations indicate that autosomal
trisomy of one of the smaller chromosomes is associated with their appearance.

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