Primitive Streak

At the beginning of the third week, a thickened linear band of epiblast, the primitive streak, appears caudally in the median plane of the dorsal aspect of the embryonic disc (Fig. 5-2B). The primitive streak results from proliferation and migration of cells of the epiblast to the median plane of the embryonic disc (Fig. 5-2D). As the primitive streak elongates by the addition of cells to its caudal end, its cranial end proliferates to form the primitive node (Fig. 5-2E and F). Concurrently, a narrow primitive groove develops in the primitive streak that ends in a small depression in the primitive node, the primitive pit (Fig. 5-2F). As soon as the primitive streak appears, it is possible to identify the embryo’s craniocaudal axis (cranial and caudal ends), dorsal and ventral surfaces, and right and left sides. Shortly after the primitive streak appears, cells leave its deep surface and form mesoblast, a loose network of embryonic connective tissue known as mesenchyme (Figs. 5-2H and 5-3B and C) that forms the supporting tissues of the embryo.

Figure 5–3 A, Dorsal view of a 16-day embryo. The amnion has been removed to expose the embryonic disc. B, Illustration of the cranial half of the embryonic disc during the third week. The disc has been cut transversely to show the migration of mesenchymal cells from the primitive streak to form the mesoblast that soon organizes to form the intraembryonic mesoderm. C, Sagittal section of a trilaminar embryo showing ectoderm (Ec), mesoderm (M), and endoderm (En). Also visible are the amniotic sac (A), the umbilical vesicle (U), and chorionic villi (CV).

(C, Courtesy Dr. E. Uthman, Houston/Richmond, Texas.)

Under the influence of various embryonic growth factors, including BMP signaling, epiblast cells migrate through the primitive groove to become endoderm and mesoderm. Mesenchymal cells have the potential to proliferate and differentiate into diverse types of cells, such as fibroblasts, chondroblasts, and osteoblasts. Recent studies indicate that signaling molecules (nodal factors) of the transforming growth factor β (TGF-β) superfamily induce the formation of mesoderm.

The primitive streak actively forms mesoderm until the early part of the fourth week; thereafter, its production slows down. The streak diminishes in relative size and becomes an insignificant structure in the sacrococcygeal region of the embryo (Fig. 5-4A to D).

Figure 5–4 Dorsal views of the embryonic disc, showing how it lengthens and changes shape during the third week. The primitive streak lengthens by the addition of cells at its caudal end; the notochordal process lengthens by the migration of cells from the primitive node. At the end of the third week, the notochordal process is transformed into the notochord.

Notochordal Process and Notochord

Some mesenchymal cells migrate cranially from the primitive node and pit, forming a median cellular cord, the notochordal process (Figs. 5-2 G, 5-4B to D, and 5-5A to C). This process soon acquires a lumen, the notochordal canal (Fig. 5-5C and D). The notochordal process grows cranially between the ectoderm and endoderm until it reaches the prechordal plate, a small, circular area of cells that is an important organizer of the head region (Fig. 5-2C). The rod-like notochordal process can extend no farther because the prechordal plate is firmly attached to the overlying ectoderm. Fused layers of ectoderm and endoderm form the oropharyngeal membrane (Fig. 5-6C) located at the future site of the oral cavity (mouth).

Figure 5–5 Illustrations of the development of the notochordal process. The small sketch at the upper left is for orientation. A, Dorsal view of the embryonic disc (at approximately 16 days), exposed by removal of the amnion. The notochordal process is shown as if it were visible through the embryonic ectoderm. B, C, and D, Median sections, at the same plane as shown in A, illustrating successive stages in the development of the notochordal process and canal. The stages shown in C and D occur at approximately 18 days.

Figure 5–6 Development of the notochord by transformation of the notochordal process. A, Dorsal view of the embryonic disc (at approximately 18 days), exposed by removing the amnion. B, Three-dimensional median section of the embryo. C and E, Similar sections of slightly older embryos. D, F, and G, Transverse sections of the trilaminar embryonic disc shown in C and E.

Some mesenchymal cells from the primitive streak and the notochordal process migrate laterally and cranially between the ectoderm and endoderm until they reach the margins of the embryonic disc. These mesenchymal cells are continuous with the extraembryonic mesoderm that covers the amnion and the umbilical vesicle (Fig. 5-2D and F). Some cells from the primitive streak migrate cranially on each side of the notochordal process and around the prechordal plate. They meet cranially to form the cardiogenic mesoderm in the cardiogenic area, where the primordium of the heart begins to develop at the end of the third week. Caudal to the primitive streak there is a circular area—the cloacal membrane—that indicates the future site of the anus (Fig. 5-6D).

The notochord is a cellular rod that:

The vertebral column forms around the notochord, which extends from the oropharyngeal membrane to the primitive node. The notochord degenerates and disappears as the bodies of the vertebrae form, but parts of it persist as the nucleus pulposus of each intervertebral disc. The notochord functions as the primary inductor in the early embryo. It induces the overlying embryonic ectoderm to thicken and form the neural plate (see Figs. 5-4B and C and 5-6A to C), the primordium of the central nervous system.

Neural Plate and Neural Tube

As the notochord develops, it induces the embryonic ectoderm over it to thicken and form an elongated plate of thickened neuroepithelial cells called the neural plate (Fig. 5-5C). The ectoderm of the neural plate (neuroectoderm) gives rise to the central nervous system and other structures such as the retina. At first, the elongated neural plate corresponds precisely in length to the underlying notochord. It appears cranial to the primitive node and dorsal to the notochord and the mesoderm adjacent to it (Fig. 5-4B). As the notochord elongates, the neural plate broadens and eventually extends cranially as far as the oropharyngeal membrane (Fig. 5-4C).

On approximately day 18, the neural plate invaginates along its central axis to form a median longitudinal neural groove that has neural folds on each side (see Fig. 5-6F and G). The neural folds are particularly prominent at the cranial end of the embryo and are the first signs of brain development (Fig. 5-7C). By the end of the third week, the neural folds have begun to move together and fuse, converting the neural plate into a neural tube (Figs. 5-7F and 5-8). Neural tube formation is a complex cellular and multifactorial process involving genes and extrinsic and mechanical factors.

Figure 5–7 Illustrations of embryos 19 to 21 days old, illustrating the development of the somites and the intraembryonic coelom. A, C, and E, Dorsal view of the embryo, exposed by removal of the amnion. B, D, and F, Transverse sections through the embryonic disc at the levels shown. A, A presomite embryo of approximately 18 days. C, An embryo of approximately 20 days, showing the first pair of somites. A portion of the somatopleure on the right has been removed to show the isolated coelomic spaces in the lateral mesoderm. E, A three-somite embryo (approximately 21 days old), showing the horseshoe-shaped intraembryonic coelom, exposed on the right by removal of part of the somatopleure.

Figure 5–8 Diagrammatic transverse sections through progressively older embryos, illustrating the formation of the neural groove, neural tube, and neural crest up to the end of the fourth week.

The neural tube soon separates from the surface ectoderm (Fig. 5-8E). The free edges of the ectoderm fuse so that this layer becomes continuous over the neural tube and the back of the embryo. Subsequently, the surface ectoderm differentiates into the epidermis of the skin. Neurulation is completed during the fourth week (see Chapter 6).

Neural Crest Formation

As the neural folds fuse to form the neural tube, some neuroectodermal cells lying along the crest of each neural fold lose their epithelial affinities and attachments to neighboring cells (Fig. 5-8A to C). As the neural tube separates from the surface ectoderm, these neural crest cells migrate dorsolaterally on each side of the neural tube. They form a flattened irregular mass, the neural crest, between the neural tube and the overlying surface ectoderm (Fig. 5-8D and E). The neural crest soon separates into right and left parts that migrate in a wave to the dorsolateral aspects of the neural tube (see Fig. 5-8F). Neural crest cells also migrate widely within the mesenchyme. Neural crest cells differentiate into various cell types (see Fig. 6-4), including the spinal ganglia and the ganglia of the autonomic nervous system. The ganglia of cranial nerves V, VII, IX, and X are partially derived from neural crest cells. Neural crest cells also form the sheaths of the peripheral nerves and the pia mater and arachnoid mater.

Vasculogenesis and Angiogenesis

Blood vessel formation in the embryo and the extraembryonic membranes during the third week may be summarized as follows (Fig. 5-9C to F):

Vasculogenesis:

Angiogenesis:

Blood cells develop from specialized endothelial cells of vessels (hemangioblasts) on the umbilical vesicle and allantois at the end of the third week (see Fig. 5-9E and F). Blood formation (hematogenesis) does not begin within the embryo until the fifth week. This process occurs first in various parts of the embryonic mesenchyme, chiefly the liver, and later, in the spleen, bone marrow, and lymph nodes. Fetal and adult erythrocytes are also derived from hematopoietic progenitor cells (hemangioblasts). The mesenchymal cells that surround the primordial endothelial blood vessels differentiate into muscular and connective tissue elements of the vessels.

The heart and great vessels form from mesenchymal cells in the heart primordium, or cardiogenic area (see Fig. 5-7A and 5-9B). Paired, endothelium-lined channels—endocardial heart tubes—develop during the third week and fuse to form a primordial heart tube. The tubular heart joins with blood vessels in the embryo, connecting stalk, chorion, and umbilical vesicle to form a primordial cardiovascular system (Fig. 5-11C). By the end of the third week, blood is flowing, and the heart begins to beat on day 21 or 22. Thus, the cardiovascular system is the first organ system to reach a primitive functional state. The embryonic heartbeat can be detected by Doppler ultrasonography during the fourth week, approximately 6 weeks after the last normal menstrual period (Fig. 5-10).

Figure 5–11 Illustrations of the development of the secondary chorionic villi into the tertiary chorionic villi. A, Sagittal section of an embryo (at approximately 16 days). B, Section of a secondary chorionic villus. C, Section of an embryo (at approximately 21 days). D, Section of a tertiary chorionic villus. By the end of the third week, a primordial uteroplacental circulation has developed.