Embryonic Development: Week 3

• The image is study notes on presomitic embryonic development, specifically the third week

Third Week of Development

• The embryo transitions from a bilaminar disc to a trilaminar disc.
• This is facilitated by gastrulation, which results in the formation of three germ layers: ectoderm, mesoderm, and endoderm.
• These three layers gives rise to different tissues and organs in the developing embryo.

Gastrulation

• Gastrulation is the process where cells from the epiblast migrate through the primitive streak, forming the trilaminar embryo.
• It happens during the third week, specifically from days 15 to 18 plus or minus one day.
• This period involves forming the primitive streak and the germ layers including the notochord.
• During this time, the embryo is called a gastrula.

Primitive Streak Formation

• The primitive streak forms early in the third week and concentrates cells in the midline of the caudal epiblast.
• The streak elongates rostrally as cells from the epiblast are added.
• The cranial end of the streak forms the primitive node or Hensen's node.
• The primitive streak establishes the embryo's polarity, marking:
  • Cranial-caudal axis
  • Dorsal and ventral surfaces
  • Right and left sides.

Molecular Regulation

• Molecular signals from the primitive node regulate cell movement during gastrulation.
• Key molecules and genes involved:
  • Wnt, Nodal, and Cordina in the posterior region for streak formation
  • Nodal, FGF-8, Lefty-1, and Pit-2 on the left side for establishing laterality
  • Slug in epiblast cells for epithelial-mesenchymal transition
  • HNF-3B in the primitive node for notochord development
  • Cordina and nogina in the notochord for neural plate formation
  • Wnt, FGF, Notch, and paraxis in paraxial mesoderm for somite formation
  • Shh in the notochord and neural tube for sclerotome differentiation
  • Wnt in the dorsal neural tube for dermomyotome formation
  • BMP-4 related to lateral mesoderm
  • VEGF, PDGF, and angiopoietin-1 in embryonic structures, key for vessel formation
  • NKX2.5 in splanchnic mesoderm for heart formation

Cell Movements

• During gastrulation, epiblast cells change shape, detach from the epiblast, and migrate.
• Cells become mesenchymal, losing cell-to-cell adhesion and gaining the ability to move freely.
• This process is facilitated by hyaluronic acid secreted by the epiblast and fibronectin for substrate adhesion.
• Some cells integrate into the hypoblast to form the embryonic endoderm, while others remain between the epiblast and endoderm to form the mesoderm.

Regression

• By the fourth week, mesoderm migration slows.
• Subsequently, the primitive streak regresses and diminishes in size.
• Residual primitive streak cells contribute to the sacrococcygeal region.
• If the primitive streak does not fully regress, it can lead to teratoma formation, most commonly in the sacrococcygeal area.

Teratoma

• Sacrococcygeal teratoma is a common congenital tumor in newborns, occurring in 1 in 35,000-40,000 births.
• Are often found in females.
• It originates from pluripotent cells from the primitive streak.
• Can contain tissues from all three germ layers.
• Lesions may be well-differentiated (mature) or undifferentiated (immature), with immature teratomas having a higher risk of malignancy.

Germ Layers

• As a result of gastrulation, the trilaminar disc comprises the ectoderm, mesoderm, and endoderm:
  • Ectoderm: forms the dorsal surface and is covered by the amniotic cavity
  • Mesoderm: forms the intermediate layer
  • Endoderm: forms the ventral surface adjacent to the yolk sac

Notochord

• The notochord is a cylindrical structure that develops during gastrulation along the embryo's longitudinal axis.
• Subsequently, the vertebral column forms around the notochord.
• It degenerates into the nucleus pulposus of the intervertebral discs.
• Key roles of the notochord:
  • Defines the longitudinal axis of the embryo.
  • Serves as the foundation for the axial skeleton.
  • Induces the formation of the neural plate, which leads to the central nervous system.

Notochord Formation

• Notochord forms during gastrulation as epiblast cells migrate through the primitive node towards the prechordal plate (forms the head organizer).
• The notochordal process develops, forming the notochordal canal that connects with the yolk sac.
• The floor of the notochordal process fuses with the endoderm.
• Openings form, creating a notochordal plate.
• The notochordal plate invaginates and becomes the definitive notochord.

Germ Layer Derivatives

• Following is a list of structures derived from the three germ layers:
  • Ectoderm- includes epidermis, hair, nails, anterior pituitary, tooth enamel, internal ear, lens, all ganglia and nerves, adrenal medulla, connective tissue, brain and spinal cord, retina and pineal gland
  • Head Mesoderm- includes skull, connective tissue, and cementum
  • Paraxial Mesoderm- includes voluntary musculature of the head, trunk, and limbs, as well as the skeleton, dermis, and connective tissue
  • Intermediate Mesoderm- includes the urogenital system
  • Lateral Mesoderm- includes connective tissue and muscle of the viscera, serous membranes, heart, blood and lymphatic cells, spleen, adrenal cortex, and the linings of the trachea, lungs, and digestive system
  • Endoderm- includes the lining of the pharynx, tympanic cavity, auditory tube, and tonsils, plus the thyroid, parathyroid, and thymus

Neurulation

• Neurulation is the process where the neural plate forms, leading to the neural tube and neural crest, which develop into the nervous system.
• Neurulation starts at the end of the third week and continues into the fourth week.
• The ectoderm overlying the notochord thickens to form the neural plate (neuroectoderm).
• The neural plate folds inward, creating the neural groove.
• The neural folds fuse to form the neural tube, while the neural crest cells separate.
• The neural tube closes during the fourth week, forming the rostral and caudal neuropores.
• Failure of neural tube closure leads to neural tube defects.
• Neural crest cells differentiate into cells of the peripheral nervous system.

Neural Tube Defects

• Neural tube defects (NTDs) result from abnormal neural tube closure.
• Examples include anencephaly and spina bifida.
• NTDs have varying occurrences, with areas of prominence reported in China and Mexico.
• Factors include genetic predisposition and environmental influences.
• Folate deficiency is a major cause, with supplementation significantly reducing the incidence.

Mesoderm Differentiation

• Mesoderm initially consists of mesenchymal cells that migrate between the ectoderm and endoderm.
• Cells form the axial mesoderm, paraxial mesoderm, intermediate mesoderm, and lateral mesoderm.
• Axial mesoderm forms the notochord.
• Paraxial mesoderm forms somites.
• Intermediate mesoderm generates the urogenital system.
• Lateral mesoderm forms the somatopleura and splanchnopleura, enclosing the intraembryonic coelom, which is key for the skeletal structure of the body

Mesoderm Development and Segmentation

• Paraxial mesoderm condenses and segments into somitomeres, arranged from head to tail.
• Around day 20, the eighth pair of somitomeres transforms into the first pair of somites.
• These mesenchymal cells form epithelial structures that segment into somites.
• Somites differentiate into:
  • sclerotome: forms vertebrae and ribs
  • myotome: forms muscles
  • dermatome: forms dermis of the skin