GASTRULATION (3 WEEK

RD

OF EMBRYOGENESIS)

BY

DR OJEWALE A.O

1
 Outlines
• Gastrulation (Intro)
• Formation of Trilaminar Embryonic Disc
• Primitive Streak (PS)
• Formation of PS
• Functions of PS

2
 Gastrulation
• It is the most characteristic event
occurring during the third week of
gestation because it forms the three
germ layers that form all the tissues and
organs of the body.
• The process of formation of three germ
layers is called gastrulation.

3
 Formation of trilaminar
embryonic disc
• During the third week, the embryoblast
acquires the form of a disc and becomes
trilaminar (i.e., consists of three layers).
From superficial to deep these layers
are: ectoderm, mesoderm, and
endoderm.

4
 The three germ layers are formed
as follows:
• First, the embryoblast differentiates into
two layers: (a) a superficial layer
consisting of flat cells called endoderm
and (b) deep layer consisting of columnar
cells called ectoderm. The embryo at this
stage is termed bilaminar embryonic
disc.
• Now, the ectoderm forms a linear
thickening in the midline of embryonic
disc called primitive streak.
5
 Cont’d
• The primitive streak gives rise to third
layer-the mesoderm-that lies between
ectoderm and endoderm. The embryo at
this stage is called trilaminar embryonic
disc.
• During the formation of the three germ
layers other embryonic structures also
develop.

6
 Primitive Streak
• It is a linear thickened band of ectodermal
cells at the caudal end of embryo in the
midline.
• It is formed due to proliferation and
migration of cells of ectoderm on the
superior surface of embryonic disc in the
midline.
• The cells forming primitive streak are
pluripotent, i.e., they have the ability to
transform into any type of cells.
7
 Cont’d
• It becomes visible on the dorsal surface
of embryonic disc on day 15 of
embryonic development as a narrow
groove flanked by a slight bulge on
either side.
• The cranial end of the primitive streak
presents a rounded and elevated area
(primitive node) surrounding a small
primitive pit.

8
Formation of primitive streak
• At the beginning of the third week, a
longitudinal ridge appears in the midline at
the caudal end of the dorsal aspect of the
bilaminar embryonic disc.
• This longitudinal ridge is called primitive
streak. The primitive streak is visible on the
dorsal aspect of the embryonic disc, i.e.,
towards the amniotic cavity as an opaque
streak, hence the name primitive streak.
9
 Cont’d
• It is formed due to proliferation of the
ectodermal cells. The ectodermal cells
proliferate and move towards the midline.
In the midline, cells from both sides heap up
to form an elevation called primitive streak.
• At the cranial end of the primitive streak,
the cells proliferate and form a rounded
elevation called primitive node/primitive
knot/Henson’s node.
• The embryonic disc elongates and becomes
pear shaped.
10
 Cont’d
• As a result of elongation of embryonic
disc, the primitive streak also elongates
along the central axis of the embryonic
disc.

11
Formation of intraembryonic mesoderm. A. Formation of primitive streak (surface view
on the left) and as seen in transverse section of embryo on the right. B. Formation of
primitive groove and migration of the cells of the primitive streak between the ectodermal
and endodermal layers to form intraembryonic mesoderm (surface view) on the left and
12
as seen in transverse section of embryo on the right.
Functions of Primitive Streak
• The primitive streak gives rise to
following structures:
 Intraembryonic mesoderm
 Septum transversum
 Notochord
 Determines the future craniocaudal axis
of the embryo
 Demarcates the embryo into left and
right halves.
13
 Fate of Primitive Streak
• The primitive streak actively forms
intraembryonic mesoderm by
ingression of its cells up to the end of the
third week of intrauterine life (IUL).
Thereafter, it regresses craniocaudally
and completely disappears by the end of
the fourth week or becomes an
insignificant structure in the
sacrococcygeal region of the embryo.

14
 CLINICAL CORRELATE
• Sacrococcygeal teratoma: Normally, the
primitive streak undergoes degenerative
changes and disappears by the end of the
fourth week of IUL. If the cells of the
primitive streak remain after the fourth
week, the pluripotent cells of the primitive
streak give rise to a large precoccygeal
tumor called sacrococcygeal teratoma. Its
large size may cause an obstructed labor
or even death of the baby.
15
 Cont’d
• The sacrococcygeal teratoma is the
most common tumor in newborns,
occurring in 1:37,000 pregnancies. It
occurs more commonly in female babies.
The tumor usually becomes malignant
during infancy and therefore must be
removed before 6 months of age.

16
 Formation of intraembryonic
mesoderm
• The cells of the primitive streak invaginate
towards the endoderm forming a groove on
its surface called primitive groove. From the
bottom of this groove, the cells of the
primitive streak spread in between the
endoderm and ectoderm to form the
intraembryonic mesoderm-the third germ
layer.
• Mode of spread of intraembryonic
mesoderm: The intraembryonic mesoderm
spreads in cranial, caudal, and lateral 17
 Cont’d
 Region of prochordal plate where the
ectoderm and endoderm are in firm contact
with each other and form the
buccopharyngeal membrane.
 Region of cloacal membrane (circular
area at the caudal end of the disc): Here,
also the ectoderm and endoderm are in an
intimate contact with each other.
 Region of notochord: Midline between the
prochordal plate and primitive knot; this
area is occupied by the notochord.
18
 Derivatives
Ectoderm
of
Mesoderm
the germ layers
Endoderm
Epidermis of skin and its Muscles: smooth, cardiac, Epithelial lining of the
derivatives such as hair, and skeletal gastrointestinal tract (GIT),
nails, sweat, and Respiratory tract, Urinary
sebaceous glands tract, Biliary tract, Auditory
tube and middle ear cavity,
Uterus and upper part of
vagina

Epithelial lining of the lower Bones and cartilages, Liver (hepatocytes)

part of the anal canal, distal connective tissue, heart,
part of the male urethra, blood vessels, and lymph
lower part of the vagina vessels.

Epithelial lining of the Epithelial lining of blood Pancreas (acinar and islet
external auditory meatus, vessels, lymph vessels, cells), Thyroid (follicular
the oral cavity and nasal body cavities, and joint cells).
cavity cavities

Lens of eye, enamel of Spleen, kidney and ureters, Parathyroid (principle and
teeth, adenohypophysis of adrenal cortex, and testes oxyphil cells).
the pituitary gland, adrenal and ovaries
medulla, and nervous tissue 19
 Formation of notochord
• A depression appears in the center of
Hensen’s node called blastopore. A
solid cord of cells grow cranially from
the bottom of blastopore between the
ectoderm and mesoderm up to the
prochordal plate and form the
notochord.

20
 Formation of Notochord
• The notochord is a midline structure that
develops in the region between the
primitive streak and the prochordal plate.
• It develops from the primitive knot
(Hensen’s node) of the primitive streak.
• It forms the central axis of the embryonic
disc and induces the formation of neural
tube.
21
 Cont’d

Dorsal view of embryonic disc showing notochord. 22

 The various stages of development of notochord are
as follows
• The cells of primitive knot of the primitive
streak proliferate to form prenotochordal
cells that move inward (i.e., invaginates) to
produce a central depression called
blastopore.
• From the bottom of the blastopore, the
prenotochordal cells of the primitive knot
migrate forward in the midline between the
ectoderm and the endoderm of the
bilaminar germ disc to form a solid cord of
cells called notochordal process or head
process. 23
 Cont’d
• The notochord increases in length by
extending caudally as the primitive streak
recedes caudally and regresses.
• The notochordal process gets canalized
to form notochordal canal. The
notochordal canal is continuous with the
blastopore. The floor of notochordal
canal fuses with the endoderm.

24
 Cont’d
• Later both the fused parts (wall of
notochordal canal and part of
endoderm) breakdown. The notochordal
canal now communicates with the yolk
sac at one end and with the amniotic
cavity at the other end. At this stage, the
amniotic cavity and the yolk sac are in
communication with each other.
• Gradually, the walls of the canal become
flattened to form a flattened plate called
notochordal plate.
25
 Cont’d
• The notochordal plate
becomes curved to
form a tube.
• The proliferation of
cells of the tube
converts it into a solid
cord of cells to form
definitive notochord.
The endoderm is
restored, and now the
notochord is completely
separated from the
Stages of formation of notochord26
 Functions of Notochord
• It forms the central axis of the
developing embryo (embryonic disc).
• It induces the formation of neural tube
from the overlying ectoderm.
• It provides central column around which
vertebral bodies and intervertebral
discs develop.

27
 Fate of Notochord
• The notochord is present in all the animals
belonging to phylum Chordata.
• In human beings, it appears only in
embryo. In later life, it disappears but its
remnants are seen in the form of nucleus
pulposus of the intervertebral discs and
apical ligament of dens of second
cervical vertebra.

28
Formation of the Neural Tube
• The process of formation of neural tube is
called neurulation.
 The neural tube is formed from the ectoderm
overlying the notochord as follows:
• The cells of ectoderm overlying the
notochord get differentiated into
specialized cells called neuroectodermal
cells.
• The neuroectodermal cells proliferate to
form a thick plate called neural plate.
29
 Cont’d
• The neural plate extends in midline from
prochordal plate to the primitive knot.
• The margins of the neural plate get elevated
(neural folds) as paraxial mesoderm
proliferates on either side of the notochord.
• This leads to the formation of neural groove
flanked by neural folds.
• The neural groove becomes deeper and
neural folds move towards midline to fuse
with each other to form a cylindrical neural
tube. 30
 Cont’d
• The fusion of neural folds (i.e., closure of
neural tube) begins in the middle and
gradually extends in cephalic and caudal
directions.
• During the closure of the neural groove, the
cells at the tips of neural folds (neural
crests) do not take part in the formation of
neural tube.
• When the surface ectoderm is restored
they form bilateral masses dorsolateral to
the neural tube, deep to surface ectoderm.
31
 Cont’d
• The cranial part of neural tube enlarges
and forms the brain while the caudal part
of neural tube remains tubular and forms
the spinal cord.

32
 Clinical Correlation
• Chordoma: This tumor arises from the
remnants of notochord.
• It is formed either in the cranial region or in
the sacral region. In the cranial region, it
is seen at the base of the cranium and has
a tendency to spread into the
nasopharynx. It commonly occurs in men
late in life, viz., over 50 years of age.
About 30% of these tumors are malignant.
33
Formation of neural tube. A. Neural plate as seen on the dorsal surface of the pear-
shaped embryonic disc. B. Horizontal sections of embryo showing various stages of
development of neural tube. 34
 Subdivisions of Intraembryonic
Mesoderm
• The intraembryonic mesoderm on either
side of neural tube divides into three
parts. From the medial to lateral side,
these are paraxial mesoderm,
intermediate mesoderm, and lateral
plate mesoderm.
• Paraxial mesoderm: The mesoderm
lateral to neural tube condenses to form
the paraxial mesoderm.
35
Subdivisions of intraembryonic mesoderm. A. As seen in embryonic disc. B. As
seen in the horizontal section of the embryonic disc 36
 Cont’d
• Intermediate mesoderm: The mesoderm
in between the paraxial mesoderm and
lateral plate mesoderm is termed
intermediate mesoderm. It is not only
intermediate in position but also
intermediate in thickness as compared
to paraxial and lateral plate mesoderms.
• Lateral plate mesoderm: The mesoderm
in the lateral part of embryonic disc
remains thin and forms lateral plate
mesoderm. 37
 Fate of Paraxial, Intermediate, and
Lateral Plate Mesoderms

 Paraxial Mesoderm
• The paraxial mesoderm undergoes
segmentation to form somatomeres and
somites.
 Development of somatomeres
 The paraxial mesoderm is a thick
longitudinal column of mesodermal
cells that lies on each side of the
notochord and the developing neural
tube. 38
 Cont’d
• The paraxial mesoderm (longitudinal
column of mesoderm) undergoes
segmentation and gets organized into
segments known as somatomeres. The
somatomeres are formed in the
craniocaudal sequence.
• The first pair of somatomeres appears in
cephalic region of the embryo and their
formation proceeds craniocaudally. Each
somatomere consists of mesodermal cells
arranged in concentric whorls around the
center of the unit. 39
 Cont’d
• Somatomeres 1–7, which are located
from cephalic to otic vesicle, do not
condense to form somites but contribute
to mesoderm of the head and neck
region, which forms all the striated
muscles in this region.
• The remaining somatomeres located
caudal to otic vesicle condense to form
well-defined cubical blocks called
somites.
40
 Lateral view of a 30-day-old embryo.
Dorsal view of a 22-day-old embryo. Seven Thirty four somites are visible
somites are visible on each side of the neural
tube 41
 Development of somites
• These are cubical blocks of mesoderm
located caudal to otic vesicle on each
side of developing neural tube.
• The somites first appear in the future
occipital region of the embryo.
• The first pair forms on day 20-a short
distance caudal to the otic
vesicle/placode.
• Subsequent pairs form in craniocaudal
sequence. Thus, cranial somites are
oldest and caudal somites are youngest.
42
 Cont’d
• About 38 pairs of somites appear
between days 20 and 30 of development
(somite period of human development).
• By the end of the fifth week, about 42
days, 44 pairs of somites are formed in
the human embryo. Out of these 4 are
occipital, 8 are cervical, 12 are thoracic,
5 are lumbar, 5 are sacral, and from 8 to
10 are coccygeal.
• The somites form visible surface
elevations on either side of the midline. 43
 Estimation of the approximate age of
embryo according to number of somites
Approximate age of Number of somites
embryo (days) (pairs)
20 1–4
21 4–7
22 7–10
23 10–13
24 13–16
25 16–19
26 19–21
27 21–24
28 24–27
29 27–30
30 30–33
44
 Cont’d
• The first pair of somites appears in the
occipital region on day 20 (vide supra)
and subsequently approximately three
pairs of somites are added each day until
the end of the fifth week. Thus, while the
somites are forming, the number of
somites provides a good index of the age
of the embryo.

45
Correlation between somites and spinal nerves
• Somites begin to form at the cranial end of
the paraxial mesoderm and continue to do so
caudally.
• In craniocaudal direction, they are termed
occipital, thoracic, lumbar, and coccygeal
somites. Caudal to the occipital region, the
number of somites corresponds to the
number of spinal nerves in the region.
• Thus, there are 8 cervical, 12 thoracic, 5
lumbar, and 5 sacral somites
corresponding to same number of spinal
46
nerves in these region.
Subdivisions of the somites 47
 Cont’d
• The number of coccygeal somites
however exceeds the number of
coccygeal nerve, but the extra
coccygeal somites degenerate.

48
Structure and fate of somites
• Each somite is triangular in shape with a
small slit like cavity in its center.
• Each somite is divided into three parts:
medial, middle, and lateral.
 The medial part is called sclerotome,
which forms vertebrae and ribs.
 The middle part is called myotome, which
forms skeletal muscles.
 The lateral part is called dermatome,
which forms the dermis of the skin.
49
 Cont’d
 Intermediate Mesoderm
• The intermediate mesoderm forms most
of the genitourinary system, e.g.,
kidneys, testes, ovaries, etc.
 Lateral Plate Mesoderm
• The lateral plate mesoderm forms body
wall and body cavities. Initially it is
involved in the formation of
intraembryonic celom.

50
 Formation of intraembryonic
celom
• The lateral plate of mesoderm of two
sides is continuous with each other
anterior to the prochordal plate (primitive
buccopharyngeal membrane).
• A large number of small cavities appear
on each side in the lateral plate mesoderm
and mesoderm anterior to the prochordal
plate.
• All these cavities coalesce (fuse) together
to form a single large horseshoe-shaped 51
 Subdivisions of intraembryonic
celom
 During the second month, the
intraembryonic celom is divided into three
parts.
• Part anterior to the prochordal plate called
pericardial cavity.
• Right and left limbs of the intraembryonic
celom called peritoneal cavities.
• Canals through which pericardial cavity
communicates with the peritoneal cavities
are termed pericardioperitoneal canals.
52
Intraembryonic celom (surface view on the left and transverse view on the right). A. Early
stage. Note it is a closed cavity. B. Late stage. Note it is communicated53 with
extraembryonic celom. IEC =intraembryonic celom; EEC =extraembryonic celom
 Formation of somatopleuric and
splanchnopleuric layers of mesoderm
• As a result of formation of intraembryonic
celom, the lateral plate mesoderm is
divided into two layers: somatopleuric
mesoderm and splanchnopleuric
mesoderm.
 Somatopleuric (parietal) layer: It lies in
contact with the ectoderm.
 Splanchnopleuric (visceral) layer: It lies in
contact with the endoderm.
54
 Cont’d
• The somatopleuric mesoderm contributes
to the development of the body wall while
splanchnopleuric mesoderm contributes
to the development of walls of the viscera
(e.g., viscera of GIT and respiratory tracts).
• The intraembryonic mesoderm lying
anterior to the pericardial cavity is called
septum transversum, which contributes to
the development of liver and diaphragm.
• The epicardium of heart develops from
splanchnopleuric mesoderm lying in front
of the prochordal plate. 55
56
 Folding of Embryo
• The folding of an embryo is a significant
event in establishment of the primitive form
of the human body.
• As a result of folding, the flat embryonic
disc becomes somewhat cylindrical
embryo.
• The folding occurs in both median and
horizontal planes due to rapid growth of
the embryo.
57
 Folding of Embryo in the Median
Plane
 The folding of embryo in the median plane
occurs as follows.
• There is a progressive increase in the length
of embryo (embryonic disc), but its head and
tail ends remain relatively close together.
Consequently, the embryonic disc bends
producing a convexity dorsally and bulges
upward into the amniotic cavity.
• With further increase in the length of
embryonic disc, the head and tail ends also
get folded on itself to form head fold, and tail
58
Folding of the embryo and formation of gut 59
 Cont’d
• As a result of formation of head and tail
folds, the head and tail ends of embryo
move ventrally.
• Due to the formation of head and tail folds,
the part of yolk sac becomes enclosed
within the embryo to form a long tubular
structure called primitive gut. The
primitive gut forms most of the
gastrointestinal tract (GIT).
• The primitive gut is divisible into three
parts: foregut, midgut, and hindgut.
60
 Cont’d
• The midgut is in wide communication
with the yolk sac through a wide channel-
the primordium of vitellointestinal duct
(yolk stalk).
• A small diverticulum arises from the
caudal part of the yolk sac and grows
into the connecting stalk attached to the
caudal end of the embryo called
allantois (allantoic diverticulum)

61
Folding of the embryo and formation of the umbilical cord 62
 Folding of Embryo in the
Horizontal Plane
• The folding of sides of the embryo forms
right and left lateral folds. The lateral
folds move medially and fuse to each other
to form the anterior abdominal wall.
However, in the center of the anterior
abdominal wall a somewhat circular
aperture remains, which represents the
future umbilicus.
• With the formation of lateral folds in
embryo, communication between midgut
and yolk sac narrows to form the 63
 Cont’d
• As the embryo folds on itself, the amniotic
cavity expands enormously and
completely surrounds the embryo. Now the
embryo freely floats in the amniotic fluid
within amniotic cavity, which serves as a
swimming pool for the embryo.
• Due to enormous expansion of amniotic
cavity, the extraembryonic celom gets
almost completely obliterated and the
amnion forms the covering of the umbilical
cord. 64
 Effects of Folding of Embryo
 These are as follows:
• Due to the formation of folds on all sides,
the flat embryonic disc becomes
cylindrical leaving an opening on the
ventral aspect called umbilical ring.
• The ectoderm forms the outer covering of
the embryo.
• The embryo becomes completely
surrounded by the amniotic cavity.
• The part of yolk sac gets incorporated in the
embryo to form the primitive gut. 65
 Cont’d
• The cranial end of primitive gut is now
separated from stomodeum by
buccopharyngeal membrane, and the
caudal end of primitive gut is separated
from proctodeum by the cloacal
membrane.
• The connected stalk (future umbilical cord)
now becomes attached to the ventral aspect
of embryo around the umbilical opening.
• The allantois now gets connected to the
terminal part of the hindgut.
• The head containing brain now forms the 66
 Cont’d
• The septum transversum and pericardial
cavity now lie on the ventral aspect of the
cranial end of the embryo, with heart tube
lying dorsal to the pericardial cavity.
• The septum transversum now lies caudal
to the primitive heart tube and pericardial
cavity.
• A depression is formed between head
bulge and pericardial bulge. It is called
stomodeum and is separated from the
cranial end of foregut by the
67
 Arrangement of structures of embryo
Folding of the embryo. A. Embryonic disc before before and after the formation of
folding. B. Embryo after folding (frontal view). head and tail folds as seen in
C. Embryo after folding (lateral view). longitudinal sections 68
 Cont’d
• Two halves of the peritoneal cavity now
fuse to form a single peritoneal cavity.

69
 Arrangement of important structures of embryo
before and after the folding in craniocaudal
Before folding of embryo direction
After folding of embryo
Septum transversum lies cranial to the Septum transversum lies caudal to the
pericardial cavity and heart tube pericardial cavity and heart tube

Heart tube lies below the pericardial cavity Heart tube lies above the pericardial cavity
(i.e., heart tube jumps
from the floor of the pericardial cavity to its
roof)
Prochordal plate Prochordal plate forms buccopharyngeal
membrane/oral membrane
Cranial part of the neural plate lies above Cranial part of the neural plate lies above
and behind the primitive buccopharyngeal and in front of buccopharyngeal
membrane membrane/oral membrane, and forms the
most cranial structure of the embryo
Yolk sac lies below the embryo Most of yolk sac is taken up with the
embryo to form primitive gut
Connecting stalk is attached at the caudal Connecting stalk is attached on the ventral
aspect of the embryo aspect of the embryo
70
Allantois is directed caudally Allantois is directed ventrally
71