Konuri's Approach to Human Embryology

1. Introduction to Embryology

Human Embryology is the study of the developmental aspect of the human organism. It encompasses the period from the stage of a single celled zygote to the stage of the birth of the baby. Human baby is nearly adult looking, semi independent that can survive in the external environment. The human gestation period is 40 weeks.

Fish and amphibians have a larval stage in their development that occurs in aquatic environment. Reptiles have large, hard shelled eggs that are laid on dry land. Mammalian embryology proceeds in a highly protected and near constant environment, inside the uterus. All animals that belong to the placntalia constantly exchange gases, nutrients and excretory substances with the maternal blood through the placenta.

The single cell zygote has everything that is needed to develop into a complete organism. The whole genome is present in every cell, but only a certain part of it is accessible to a specialized cell. The zygote expresses the whole genome in an orderly and sequential fashion.

Zygote is formed by the union of the ovum and sperm. Sperm contributes only the nucleus, whereas the nuclear material as well as the cytoplasm is provided by the ovum. Ovum is asymmetrical to start with. This asymmetry, as it increases during growth and development, is the basis of cellular differentiation.

A cell can be defined as a compact expression of the complexity of molecular interaction in a spatio-temporal framework. Information is coded in two ways in a cell – analog and digital. Digital information is coded by the nucleic acids and analog information by the protein networks. When a cell divides, the information that is encoded in a cell is symmetrically as well as asymmetrically distributed. The information in the nucleic acids is symmetrically distributed, whereas that is present in the protein networks is asymmetrically distributed. After n number of divisions this asymmetry gives rise to a new type of cell from an old type, which is called cellular differentiation.

Throughout embryology we will be seeing one cell (or a group of cells) giving rise to two types of cells. The fate of a cell is decided by its date and place of birth. The central dogma of molecular biology is classically expressed in the following words: DNA – RNA – protein. But it should not be understood as a one way interaction. The genetic material inside the nucleus is constantly influenced by the protein networks of the cytoplasm. The cell, in turn, is influenced by its environment, by the transcriptioin factors present in its environment. One cell is influenced by another, a concept of induction classically demonstrated by Speman’s experiments.

A mammal cannot be defined by the mere presence or absence of the mammary gland, it is much more. Mammals are characterized by the presence of uterus and mammary gland, palate and orthodontic teeth, diaphragm, hair, an advanced locomotion, four chambered heart and above all a highly developed cerebral cortex. Cerebral cortex is the most important of all these features. These features are seemingly isolated and unconnected but they are inherently interconnected. The evolution of a class of animals should be studied at a depth to unravel the genetic program behind it.

Form, function and development should be understood as a continuum. Most of the gross anatomical details of the adult organism can be explained utilizing data obtained from embryological studies. Each of the three cords of the brachial plexus divide into an anterior and a posterior division. This is because of the division of the corresponding myotomes into a flexor and an extensor part. Metanephric kidney develops in the pelvis and ascends into the lumbar definitive position, an embryological fact that explains all the relations of the kidneys and their differences on both sides. The innervation of the tongue can never be understood without resorting to an embryological explanation.

Most of the neuroanatomical details need a thorough understanding of embryology. The location of the various cranial nerve nuclei and so their applied significance in clinical neurology gains meaning and insight only through embryological interpretation. Understanding the C shaped rotation of the telencephalon and its implications not only gives insights but an immense satisfaction of mastering the otherwise intimidating subject.

Most of the congenital anomalies have an embryological reason. Understanding the embryological basis of these anomalies will not only explain but also help us predicting the patterns and aid us in planning appropriate surgical procedures.

The human gestation period is 40 weeks from the date of last menstrual period. This is only an approximation because at this time of menstrual period there is no ovulation and so no zygote. Ovulation and so fertilization occurs around the fourteenth day of menstrual period. But the time of fertilization is difficult to make out in a clinical setting. Gynecologists conveniently calculate the gestational period from the first day of the last menstrual period. This is called the obstetrician’s gestational age. The embryological ae will be two weeks less than this.

Many embryology books follow the chronological order to describe the developments. This is a very tedious method in my experience. I tell the story in an interesting and curious way and followed some of the chapters by a table of chronology at the end. I wish first year students study the fantastic and fascinating subject of embryology and use it to master gross anatomy.

For the Inquisitive Mind

All physical processes, including biological should be studied from the perspective of evolution and duality.

The axiomatic statement that ontogeny repeats phylogeny is a compact expression of developmental biology from the perspective of organic evolution. The emergent properties of the system in a spatio-temporal framework are the compact expressions ofquantitative development leading to qualitative development through the the interplay of opposites and their mutual transformation. Biological systems are characterized by a series of such emergent properties. The more complex a system in the evolutionary scale, more are the varieties and number of such emergent properties. The emergent properties are always looked upon from the framework of structure function relations.

When an emergent property is exhaustively utilized for its growth and development, that it is it has reached its zenith of development is preserved in the form of a permanent structure. The inadequacy of such properties in meeting the newly emerging challenges of environment has become a stimulus for its further development over a critical period of time and space. This has given rise to new emergent properties (phase transitions) through the phenomenon of quantitative development leading to qualitative development.

The critical amount of quantity defines the necessary spatial and temporal parameters for the emergence of new qualities. Thus the biological systems are characterized by a series of stratified stabilities which are nothing but the preserved states of its previous developments, which could address the partially adequately to evolve an adaptive behavior. The inadequacy of which is an eternal source and stimulus of its never ending growth.

The duality of the process can be elaborated in the following framework of studies. The interplay of passive and active process, of analog and digital molecular networks, the interplay of stochasticity and determinism, of noise and signal, of symmetry and asymmetry.

The organization of a system predominantly through a passive process fits well into the principles of optimization from the perspective of energy expenses. The organization of the dynamics of a system both in terms of its rapidity and duration is addressed predominantly through an active process. In the overall interplay of passive and active process the predominance of passive mechanism in the emergence of phase transitions fits well in the evolutionary process of the universe from physical to chemical and from chemical to biological world.

The stochastic process in a biological system is nothing but a manifestation of passive process. The emergence of order (emergent properties and phase transitions) is the outcome of a random process. The emergence of order is a manifestation of a random process taking place in a critical spatial and temporal domain. The stabilizations of such orders is a manifestation of an active process. Many examples can be quoted to substantiate these basic statements.

The spontaneous folding of protein in an orderly manner is to decrease of entropy, which demonstrates classically the emergence of order from disorder. But the stabilization of such evolved orderly folding is taking place through the expense of energy through ATP. This is well understood today in the liquid crystal behavior of proteins.

It is not only proteins, all biomolecules are in a liquid crystal state. Another example that substantiates the above statement is the genesis of membrane potential across the biological cell membrane is predominantly by a passive process, i.e. due to the diffusion of electrolytes (potassium predominantly) but the stabilization of such electrical potentials is due to the active mechanism operating through the sodium potassium pump.

With this perspective we can proceed to the study of embryology at a depth.

2. Gametogenesis &

Fertlization

Gametogenesis

The body of an adult organism consists of two types of cells – somatic cells and gametes. Somatic cells are diploid whereas the gametes are haploid in their chromosomal number. Gametes are produced in the male and female gonads, i.e. testis and ovary respectively. Somatic cells are produced by mitotic cell division, whereas gametes are produced by meiotic cell division.

Mitosis produces Somatic cells

Meiosis produces germ cells

Cell Division

All multicellular forms of life are characterized by cell division. Cells reproduce by cell division. Sexual reproduction brought in two types of cell division- mitosis and meiosis. All somatic cells divide by mitosis whereas gametes are formed through another type of cell division called meiosis. Mitosis produces two similar cells that have the same diploid number of chromosomes. Meiosis gives rise to four cells that have haploid number of chromosomes. Moreover they give rise to male and female gametes.

Diploid state is a cell state in which there are two copies of each chromosome. In meiosis one copy of each chromosome in a set is allotted to each daughter cell and so the chromosome number is exactly halved. For this reason, meiosis is also called a reduction division. Fertilization restores the diploid state. In mitosis, each chromosome is split longitudinally into two halves and each daughter chromosome is assigned to one daughter cell. This mechanism of division will not lead to reduction of chromosome number.

Mitosis

Mitosis produces genetically identical daughter cells

Mitosis is the type of cell division that occurs in all somatic cells including the cells of the embryo. Mitosis does not lead to reduction of the number of chromosomes. So, mitosis involves the following processes: synthesis of DNA, doubling of the chromosomes, allotment of these chromosomes to the daughter cells and finally division and allotment of cytoplasm. From the standpoint of cell division, a cell has two phases a phase of cell division and an interphase. The division phase or mitotic phase is divided into the prophase, metaphase, anaphase and telophase.

A cell has two phases:

Division phase and Interphase

Interphase is again divided into G1 (first gap) phase, S (synthesis) phase and G2 (second gap) phase. G1 and G2 are growth phases, while S phase is the phase of DNA synthesis. During all three phases the cell grows by producing more and more proteins and cytoplasmic organelles, but DNA is synthesized only during the S phase. Interphase is the longer phase, usually ten times as long as the mitotic phase.

DNA is synthesized only during the S phase

Prophase

Prophase is the first preparatory phase of cell division. In this phase the nuclear material is organized into discrete pairs of chromosomes. The number of chromosomes is characteristic of each species. Humans are characterized by the presence of 23 pairs of chromosomes in the diploid state. Each chromosome has two chromatids joined at a particular place called centromere. Now the chromosome is longitudinally split to give rise to four chromatids. Meanwhile the nuclear membrane disappears.

Prophase is characterized by the appearance of Chromosomes

Fig 1. Mitosis

Metaphase

Metaphase is the phase of formation of metaphase plate. The two centrioles move to the opposite poles of the cell. They produce a number of microfilaments that pass from one centriole to another. These filaments form the spindle. These are attached to the centromeres of the chromosomes. The chromosomes are now positioned in the center on the equator of the cell called the metaphase plate.

Metaphase is characterized by the Metaphase plate

Cells have tetraploid DNA but diploid chromosomes

Anaphase is the phase of doubling of the chromosome number. The centromere of each chromosome splits into two to form two separate chromosomes. Now the cell has a tetraploid number of chromosomes and tetraploid DNA content. The spindle pulls the chromosomes to each poll of the