17.12: Organogenesis

In the initial eight weeks of gestation, the developing embryo successfully establishes the rudimentary structures of all its organs and tissues derived from the three primary germ layers: ectoderm, mesoderm, and endoderm. This process is aptly named organogenesis. 

Following gastrulation, the CNS develops through neurulation, starting with the thickening of neuroectodermal tissues into the neural plate. By the fourth week, these tissues fold upward to form neural folds, which converge to create the neural tube, positioned atop the notochord. This tube later evolves into the brain and spinal cord, with the notochord becoming the nucleus pulposus of intervertebral discs. Concurrently, somites form on either side of the neural tube, differentiating into the axial skeleton, skeletal muscles, and dermal tissues. By the fifth week, the anterior neural tube expands and subdivides into vesicles that will become the brain.

Figure 10 | Neurulation – An establishment of the future central nervous system and skeleton | ¹⁸ This step-by-step diagram illustrates the process where neuroectodermal tissues differentiate into the neural plate, which then folds to form the neural folds and eventually converges to create the neural tube. The roles of the notochord and neural crest cells in developing the central nervous system, peripheral nervous system, and axial skeleton are also depicted.

During early development, the embryo undergoes folding to form a C-shaped structure with distinct head and tail regions (Figure 11). Lateral folding and folding at the head and tail partially surround the yolk sac, creating a tube called the primitive gut, lined with endodermal cells. Simultaneously, the amniotic sac envelops the developing embryo.

Figure 11 | Embryonic folding and the formation of the primitive gut | ¹⁹ This diagram illustrates the process of embryonic folding, showing how the initially flat embryonic disc folds laterally and at the head and tail ends to form a C-shaped structure. This folding also results in the partial surrounding of the yolk sac, leading to the formation of the primitive gut tube, lined with endodermal cells.

Similar to the CNS, the heart in the embryo begins as a tubular structure establishing connections with the chorionic villi through a network of capillaries. The cells within this nascent tubular heart possess remarkable electrical conduction and contraction abilities. While the heart's development initiates in the early part of the fourth week, it only begins pumping embryonic blood about a week later. This delay coincides with the commencement of red blood cell production by the oversized liver. The embryonic liver temporarily undertakes this role until the bone marrow takes over the responsibility of blood cell production.

Over weeks 4 to 5, crucial embryonic developments include the formation of eye pits, the emergence of limb buds, and the establishment of the fundamental components of the pulmonary system. During the sixth week, uncontrolled movements of fetal limbs become observable. Simultaneously, the rapid development of the gastrointestinal system exceeds the available space in the embryonic abdomen, leading to the temporary looping of the intestines into the umbilical cord. Moreover, paddle-shaped hands and feet gradually transform, with the process of apoptosis contributing to the disintegration of tissues between the fingers, eventually giving rise to well-defined fingers and toes.

As development progresses into the seventh week, the facial structure takes on increased complexity, featuring the presence of nostrils, outer ears, and lenses (Figure 12). By the eighth week, the embryonic head is nearly as substantial as the rest of the body, and all the major structures of the brain have taken their rightful place. Although external genitalia are apparent at this stage, distinguishing between male and female embryos remains challenging. Additionally, the embryonic skeleton begins to transform cartilage into bone through ossification. 

Figure 12 | Embryo at 7 Weeks | ²⁰ An embryo at the end of seven weeks of development is only 10 mm in length, but its developing eyes, limb buds, and tail are already visible.

From weeks 9 to 12 of fetal development, the brain experiences continued expansion, the body elongates, and the process of ossification advances. The fetus begins to exhibit frequent movements, albeit in a jerky and uncoordinated manner. The role of erythrocyte production, previously managed by the embryonic liver, is gradually assumed by the bone marrow. Additionally, the liver commences the secretion of bile. The fetus actively circulates amniotic fluid by swallowing it and producing urine. By this stage, the eyes are substantially developed, though the eyelids remain fused shut. The fingers and toes commence the formation of nails. 

The period spanning weeks 16 to 20 of fetal development is marked by a substantial increase in body weight. The axons of the spinal cord commence the process of myelination, the fetus develops eyelashes, and the previously fused eyelids are now capable of being opened and closed. The lungs initiate the production of surfactant, supporting proper expansion upon birth. For male fetuses, the testes descend into the scrotum near the conclusion of this stage. 

Throughout weeks 31 to birth, the fetus continues to accumulate subcutaneous fat, promoting the development of the hypodermis. Simultaneously, the skin undergoes a transformation from red and wrinkled to soft and pink. The previously present lanugo, a silky hair covering, is shed, and the nails extend to the tips of the fingers and toes.²¹

 

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