Embryonic Development: Week 3

3rd Week of Development Overview

• Embryonic development during the third week involves the appearance of the primitive streak, development of the notochord, and differentiation of the three germ layers.
• The third week corresponds to the week of the first missed menstrual period, about 5 weeks after the last menstrual period.
• Cessation of menstruation is often the first sign of pregnancy.

Gastrulation

• Gastrulation transforms the bilaminar embryonic disc into a trilaminar embryonic disc.
• The trilaminar disc's three germ layers which are ectoderm, endoderm and mesoderm give rise to specific tissues and organs.
• Gastrulation marks the beginning of morphogenesis, which is the development of the body's form and structure.

Primitive Streak

• The primitive streak appears on the dorsal side of the embryonic disc at the start of the third week.
• A thickened linear band results from epiblast cell proliferation and migration towards the embryonic disc's median plane.

Axis Determination

• The appearance of the primitive streak allows identification of the embryo's craniocaudal axis (cranial and caudal ends), along with dorsal and ventral surfaces, and right and left sides.

Primitive Node and Groove

• The primitive streak elongates through the addition of cells at its caudal end, while its cranial end proliferates, forming the primitive node.
• A narrow primitive groove develops within the primitive streak.
• The primitive groove ends in a small depression called the primitive pit, located in the primitive node.

Germ Layer Formation

• After the appearance of the primitive streak, epiblast cells migrate through the primitive groove to form the endoderm, then the mesoderm, creating a loose network of embryonic connective tissue called mesenchyme.

Trilaminar Embryo

• A sagittal section of a trilaminar embryo shows ectoderm (Ec), mesoderm (M), endoderm (En), the amniotic sac (A), the umbilical vesicle (U), and chorionic villi (CV).

Embryonic Growth Factors

• Various embryonic growth factors induce epiblast cells to migrate through the primitive groove, forming the endoderm and mesoderm.

Mesenchymal Cells

• Mesenchymal cells can proliferate and differentiate into diverse cell types like fibroblasts, chondroblasts, and osteoblasts.
• The primitive streak actively forms mesoderm, until the early fourth week.

Notochordal Process

• Mesenchymal cells migrate cranially from the primitive node and pit, forming the notochordal process, a median cellular cord.
• This process soon develops a lumen, known as the notochordal canal.

Streak Regression

• As the embryo grows, the primitive streak diminishes in size, becoming an insignificant structure in the sacrococcygeal region.

Prechordal Plate

• The notochordal process grows cranially between the ectoderm and endoderm, reaching the prechordal plate.
• The prechordal plate is a small area of cells, serving as a crucial organizer for the head region.
• Fused ectoderm and endoderm layers create the oropharyngeal membrane, marking the future site of the oral cavity (mouth).

Cloacal Membrane

• A circular area caudal to the primitive streak marks the location of the cloacal membrane, indicating the future site of the anus.

Canal Fusion

• The notochordal canal fuses with the degenerating endoderm.
• The neuroenteric canal is formed as a result.

Notochord Formation

• Notochordal foldings close, forming the notochord, which separates from the underlying endoderm.

Notochord Composition

• The notochord is a cellular rod that defines the embryo's axis and gives it rigidity.
• It serves as the basis for developing the axial skeleton (bones of the head and vertebral column).
• The notochord indicates the future sites of the vertebral bodies.

Vertebral Development

• The vertebral column forms around the notochord.
• As vertebrae develop, the notochord degenerates and disappears, but remnants persist as the nucleus pulposus of each intervertebral disc.

Mesodermal Continuity

• Mesenchymal cells are continuous with the extraembryonic mesoderm, covering both the amnion and the umbilical vesicle.

Cell Migration

• Mesenchymal cells migrate laterally and cranially between the ectoderm and endoderm, reaching the margins of the embryonic disc.

Cardiogenic Mesoderm

• Cells from the primitive streak migrate cranially on each side of the notochordal process and around the prechordal plate.
• These cells meet cranially to form the cardiogenic mesoderm in the cardiogenic area, where the heart primordium begins to develop at the end of the third week.

Notochord Function

• The notochord functions as the primary inductor in the early embryo.
• It induces the overlying embryonic ectoderm to thicken and form the neural plate, which is the primordium of the central nervous system (neurulation).

Neural Tube Formation

• Neurulation involves forming the neural plate and neural folds, followed by the closure of these folds to create the neural tube.
• These processes are completed by the end of the fourth week, when closure of the caudal neuropore occurs.

Process of Neurulation

• As the notochord develops, it induces the overlying embryonic ectoderm to thicken and form an elongated neural plate of thickened neuroepithelial cells.
• The ectoderm of the neural plate (neuroectoderm) gives rise to the central nervous system (CNS) which incorporates the brain and spinal cord, and other components like the retina.
• The neural plate appears cranial to the primitive node and dorsal to the notochord.
• As the notochord elongates, the neural plate broadens and extends cranially.

Neural Groove

• Around day 18, the neural plate invaginates along its central axis, forming a median neural groove with neural folds on each side.
• Neural folds are the first indication of the brain development.
• By the end of week three, the neural folds move together and fuse which converts the neural plate into the neural tube, and the primordium of the brain vesicles and the spinal cord.
• The neural tube separates from the surface ectoderm as the neural folds meet.
• The free edges of the ectoderm fuse which makes this layer continuous over the neural tube.
• The surface ectoderm differentiates into the epidermis of the skin.
• Neurulation is completed during week four.

Neural Crest Cells

• Neural crest cells differentiate into different cell types, including spinal ganglia, autonomic nervous system ganglia, cranial nerve ganglia (V, VII, IX, and X partially), peripheral nerve sheaths, and the pia and arachnoid mater.

Somite Development and Formation

• As the notochord and neural tube form, the intraembryonic mesoderm makes a thick column of paraxial mesoderm.
• Each column is continuous with intermediate mesoderm, which gradually thins into a layer of lateral mesoderm.
• Toward the end of the third week, the paraxial mesoderm differentiates and divides into paired cuboidal bodies called somites, on each side of the neural tube.
• Somites form surface elevations on the embryo.

Somites Differentiation

• Somites give rise to most of the axial skeleton, associated musculature, and adjacent dermis of the skin.

Allantois Development

• Around day 16, the allantois appears as a small diverticulum (outpouching) from the caudal wall of the umbilical vesicle into the connecting stalk.
• The allantois participates in early blood formation and it is also associated with the urinary bladder.
• The blood vessels of the allantois become the umbilical arteries and veins.

Intraembryonic Coelom

• The intraembryonic coelom which is the body cavity, first appears as small, isolated coelomic spaces in the lateral intraembryonic mesoderm and cardiogenic mesoderm.
• These spaces merge to form a single cavity which is the intraembryonic coelom
• The coelom divides the lateral mesoderm into two layers: the somatic or parietal (somatopleure) layer continuous with the extraembryonic mesoderm covering the amnion, and the splanchnic or visceral (splanchnopleure) layer continuous with the extraembryonic mesoderm covering the umbilical vesicle.

Coelom Division

• During the second month, the intraembryonic coelom is divided into three body cavities which are the pericardial cavity, pleural cavities, and peritoneal cavity.

Early Cardiovascular System Development

• At the end of the second week, the embryo receives nutrition from the maternal blood through diffusion within the extraembryonic coelom and umbilical vesicle.
• Early formation of the cardiovascular system allows for the transport of oxygen and nourishment to the embryo from the maternal circulation through the chorion.

Vasculogenesis

• Blood vessel formation (vasculogenesis) begins at the start of the third week in the extraembryonic mesoderm of the umbilical vesicle, connecting stalk, and chorion.
• Vasculogenesis begins in the chorion.
• By the end of the third week, a primordial circulation has developed.
• Mesenchymal cells differentiate into angioblasts (vessel-forming cells) that cluster to form blood islands.
• Small cavities appear inside the blood islands.
• Angioblasts flatten to form endothelial cells around the cavities in the blood islands which creates the primordial endothelium.
• The primordial endothelium fuse to make networks of endothelial channels.

Angiogenesis

• Vessels sprout via endothelial budding into adjacent nonvascularized areas and fuse with other vessels.
• Blood cells develop from hematopoietic stem cells or blood vessels as they grow on the umbilical vesicle and allantois at the end of the third week.
• The heart and great vessels develop from mesenchymal cells in the heart primordium or cardiogenic area.
• Paired, endothelium-lined channels which are the endocardial heart tubes form during the third week and fuse to make the primordial heart tube.
• The tubular heart connects to blood vessels in the embryo, connecting stalk, chorion, and umbilical vesicle to form the primordial cardiovascular system.
• Blood begins flowing and the heart begins to beat on day 21 or 22.
• The cardiovascular system is the first organ system to fully function in a primitive state.
• An embryonic heartbeat can be identified during the fourth week usually 6 weeks after the last normal menstrual period.

Development of Chorionic Villi

• Secondary chorionic villi cover the entire surface of the chorionic sac.
• After they appear at the end of week 2, the primary chorionic villi begin to branch.
• In the third week, mesenchyme grows into the primary villi, forming a core of mesenchymal tissue.
• Mesenchymal cells differentiate into both capillaries and blood cells.
• Once capillaries are present, the villi are tertiary chorionic villi.
• Oxygen and nutrients in maternal blood pass through the walls of the villi to get to the embryo and carbon dioxide and waste pass from the embryo blood into the maternal blood for removal.