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Education: Embryological Development

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Embryology is the field of science that studies the progression of a fertilized egg, as it develops into a fetus over the course of the first 8 weeks of pregnancy. In this 8-week period the fertilized egg becomes 10,000 times larger, going from 2 cells (one sperm cell + one egg cell) to the size of a raspberry. At 8 weeks the fertilized egg is growing at a rate of 100,000 cells per minute and has developed into an almost fully recognizable human, now called a fetus with fingers, hands, arms, toes, feet, legs, head, nose, mouth, eyes, and ears.

Human Fetus
Embryonic Development: Early zygote development Human Fetus
(Source: (Source:

Once a sperm cell successfully fuses with an egg, it penetrates into the eggs nucleus and the 2 cells, for an instant, become one cell. From this point on, the fertilized egg, also called a “zygote” contains genetic material from both the mother and father. The zygote contains maternally derived mitochondria for energy production and proteins necessary for the initial stages of cell division. Within the first two weeks, the zygote goes through a series of specialized cell divisions, growing from a single cell into the multicellular blastocyst which resembles a hollow ball with a clump of cells on the inside. Through a process termed hatching, the blastocyst implants into the uterine wall establishing physical contact with the motherZs body. The clump of cells on the inside of the blastocyst, called the inner cell mass, go on to form all the cells of the embryo while the outer cells of the blastocyst wall form into the placenta that, performs all the functions of organs in an adult throughout the pregnancy.

Development from the zygote into a fetus is characterized by defined genetic and epigenetic programs which direct protein expression, physiological processes which drive energy metabolism for both sustenance and development and morphological stages characterized by the appearance and growth of the germ layers from which all tissues, organs and appendages develop.

During the third week, the tri-laminar embryo forms through gastrulation, characterized by the appearance of the primitive node. From this location, cells migrate to establish the primitive streak and the left-right axis of the developing embryo. The most prominent structure to develop during this time is the notochord found along the central axis of the embryo. The notochord secretes a signaling protein called Sonic Hedge-Hog and drives the morphogenesis of the neural tube, the somites and various organs. At this stage, the three germ layers, ectoderm, mesoderm and endoderm, are established from which all the various tissues and organs develop.

Germ Layers
Germ Layers

Germ Layers

Within each of these 3 layers, unique genetic and epigenetic programs are activated resulting in the appearance of morphogenetic fields that are characterized by the expression of discrete factors, or proteins, dictating tissue and organ formation.  Once the morphogenetic fields are established, the zygote goes through a series of morphological changes as the internal organs develop and grow in size. Approximately 8 weeks after fertilization, the fetus has developed and the human form is fully recognizable.

Embryologic development of hands

During the fifth week anatomically distinct Limb Buds, or Wolff’s structures, have formed on the 2 sides of the zygote. Initially directed by the HOX gene family, then followed by the expression of the TBX-4 gene, the arms and hands are formed over the course of 3 weeks.  Disruptions in either of these genes, or any of the several signaling pathways involved, causes a variety of deformities of the arms and/or hands. Development of the arms and hands can be described in 4 stages:

  1. The initial appearance of the limb bud,
  2. The paddle stage or flatting of the most distal portion of the growing limb,
  3. The plate stage or expansion of the paddle and finally
  4. Rotation of the flattened paddle.

The hand forms from the end of the growing limb initially resembling a paddle. Within this paddle-like structure, soft, cartilaginous digital rays begin to form and eventually develop into fingers. At the same time, the blood vessels, nerves, muscles and connective tissue are formed into the structure we recognize as a hand. Until this point, the skin between the fingers remains webbed, much like a frog or other amphibians. Once ossification of the cartilaginous digital rays begins, a series of apoptotic, or death signals, result in the death of the cells making up the web, and the fingers are then fully separated.

Developing human hand
(Sources: [1], [2], [3])

Embryologic development of the face

As complicated as the hand may seem in both structure and function, it pales in comparison to the face and skull. Almost all of our interaction with the outside world goes through the senses contained in specialized organs found in the face and head: sight, sound, taste and smell. As the brain develops, concomitant appearance of precursors to the variety of facial nerves, and the cells from which they develop, initiate a complex array of signaling programs which pattern and direct the development of the face, eyes, nose and ears. As with the limb bud, HOX genes drive the overall development of craniofacial structures. And also like in the limb bud, during development the craniofacial structures are highly sensitive to any disruptions in signaling or mutations.  The development of the face is realized through a series of convolutions and involutions resulting in the familiar features that together we recognize as a face. By the 8th week, the facial structures are well developed and the face is  clearly recognizable as a human face.

Developing human face
(Sources: [1], [2])

Embryology and electrical currents

A renaissance in the field of bioelectric chemistry is providing novel information about the vitally important role that bioelectricity plays in the early stages of development. Although its importance has been appreciated for at least 100 years, only recently have the advances in modern technology allowed scientist to measure and control the very small currents (pico amperes) and voltages (millivolts) that exert powerful effects on development and homeostasis. Bioelectricity can be observed in at least two forms: as an electric field which originates from outside of cells and tissues (EF), and as voltage differences between the outside and inside of the cell, established by the flow of ions through pores in the cell wall. These latter are responsible for establishing a membrane voltage (Vmem) differential.  Ultimately, EF and Vmem, trigger specific gene expression programs that are controlled and coordinated in parallel. Studies on frog and salamander embryos have clearly established regions and patterns of varying EF and Vmem strengths which, when altered, block or severely alter the development of a growing embryo.

Embryology and regenerative medicine

Regenerative medicine has its foundations in the field of embryology, as genetic, epigenetic, morphogenetic and bioelectric programs that drive development in utero are most likely similar to those that could be used to regrow a hand or a face. The question is, how does modern science reactivate these programs in an adult organism? It is not simply a linear system: to regrow a hand, multiple parallel systems must be activated, deactivated and controlled in precise spatio-temporal conditions.  Thanks to recent advances in biotechnology, we now have a wealth of information about the genome, transcriptome, proteome, metabolome. Within this information lies the solution to regrowing hands and faces. To make use of this information in such a way that it can be used to solve this puzzle it must be integrated into a comprehensible new paradigm.

Human Fetus

For an in depth look at each stage of embryological development, the reader is referred to the Carnegie staging system.