Week 3 & 4 Embryology PDF

Week 3: Formation of the Trilaminar Germ Disc (Gastrulation) 1. Primitive Streak and Body Axes Formation: o Primitive Streak appears on the Epiblast’s dorsal surface, marking the start of gastrulation and defining the Cranial-Caudal Axis. o Primitive No...

Week 3: Formation of the Trilaminar Germ Disc (Gastrulation) 1. Primitive Streak and Body Axes Formation: o Primitive Streak appears on the Epiblast’s dorsal surface, marking the start of gastrulation and defining the Cranial-Caudal Axis. o Primitive Node and Oropharyngeal Membrane appear; the Oropharyngeal Membrane will form the mouth, and the Primitive Streak will guide cell migration. o Primitive Streak and Primitive Node guide cell migration and differentiation that establish the three primary germ layers. 2. Formation of Three Germ Layers via Gastrulation: o Cells of the Epiblast migrate through the Primitive Streak, forming: ▪ Endoderm: Replaces Hypoblast cells from inner layer. ▪ Mesoderm: Fills the space between the Endoderm and Ectoderm. ▪ Ectoderm: Forms from the remaining Epiblast cells which form the outer layer. 3. Molecular Regulation of Embryonic Axes: o Cranial-Caudal Axis: ▪ Caudalizing factors (Nodal, BMP4, WNT) released at the Primitive Node (caudal end) ▪ Cranializing factors (OTX2, LIM1, HESX1, CER-I) are released by the Anterior Visceral Endoderm (AVE), inhibiting caudalizing factors in the cranial region. o Dorsal-Ventral Axis: ▪ BMP4 is present in the entire embryo, promoting ventral development. ▪ However, Goosecoid, Chordin, Noggin, Follistatin, and Nodal act as BMP4 inhibitors in the dorsal region, allowing dorsal structures to formLeft-Right Axis is defined through specific gene expression at this stage.Left-Right Axis: As cells migrate and differentiate, they establish the left-right axis. o Left-Right Axis: As cells migrate and differentiate, they establish the left-right axis. 4. Epithelial-Mesenchymal Transition (EMT): o Epiblast cells undergo EMT, transitioning to mesenchymal cells that can migrate and form the three germ layers. o EMT Process: Involves loss of cell adhesion (e.g., E-cadherin), allowing cells to migrate and form the mesoderm and endoderm. 5. Endoderm and Mesoderm Formation:  o First Wave of Migration: Cells replace the Hypoblast to form the Endoderm. o Second Wave: Migrating cells create the Mesoderm between the Ectoderm and Endoderm layers. o Prechordal Cells and Prechordal Mesoderm form in cranial regions, which will help form the early head region and the Notochord. Week 3-4: Mesoderm Differentiation and Notochord Development 1. Mesodermal Layer Specialization: o Paraxial Mesoderm: Forms somites, which later differentiate into myotomes (muscles), sclerotomes (axial skeleton), and dermatomes (dermis). o Intermediate Mesoderm: Develops into structures of the urogenital system. o Lateral Plate Mesoderm divides into: ▪ Somatic Mesoderm: Forms limb skeleton and body cavity linings. ▪ Splanchnic Mesoderm: Develops into the heart, blood cells, and gut walls. 2. Notochord Formation: o Primitive Node and Primitive Streak: These structures guide cells from the Epiblast to migrate inward. o First Wave of Cell Migration: - Prechordal Cells and Prechordal Mesoderm: ▪ Cells that migrate cranially from the Primitive Node through the Primitive Streak form the Prechordal Mesoderm. ▪ The Prechordal Mesoderm migrates further cranially and differentiates into Prechordal Cells, located near the future head region. ▪ These cells contribute to the head's formation and play a crucial role in inducing the differentiation of the forebrain. - Prenotochordal Process and Formation of the Notochord: ▪ Following the prechordal cells, more cells migrate cranially from the Primitive Node to form the Prenotochordal Process, which elongates toward the cranial region beneath the epiblast layer. ▪ The Prenotochordal Process then merges with the endodermal layer to form a transient structure called the Notochordal Plate.  ▪ As the embryo matures, the Notochordal Plate separates from the endoderm, rolls up, and forms the Notochord, a rod-like structure that provides rigidity and structural support. ▪ The Notochord establishes the embryo's longitudinal axis, facilitates elongation, and acts as a signaling center, releasing factors that induce the overlying ectoderm to form the Neuroectoderm, the precursor to the nervous system. Days 17-21: Formation of Neural Plate and Neurulation 1. Formation of the Neural Plate and Neural Tube: o Neural Plate: Induced by signals from the Notochord, forms at the cranial end by Day 18. o Neural Tube Formation: The Neural Plate folds to create the Neural Tube, the precursor to the brain and spinal cord. 2. Neural Crest Cells and Neural Tube Closure: o By Day 21, the Neural Tube closes starting cranially and progressing caudally. o Neural Crest Cells: Form at the edges of the neural folds and migrate to form various structures, such as melanocytes, ganglia, Schwann cells, and components of the adrenal medulla. o By Day 21, the Neural Tube begins closing cranially, then caudally. Day 21-28: Completion of Neural Tube Closure and Organ Primordia 1. Completion of Neural Tube and Early Organ Formation: o By Day 28, the Neural Tube fully closes, with anterior and posterior neuropores sealing. o Initial organ structures, like otic placodes (future ears), pharyngeal arches, and pericardial bulges (future heart) become visible. 2. Derivatives of Germ Layers: o Ectodermal germ layer: epidermis, hair, nails, mammary glands, sebaceous glands, cornea, and oral epithelium, central nervous system, including the brain, spinal cord, eyes, and posterior pituitary, peripheral nervous system, cranial ganglia, parts of the skull, teeth, and connective tissues of the face, along with sensory ganglia, autonomic ganglia, melanocytes, and adrenal medulla. o Mesodermal layer: Differentiates into muscles, bones, urogenital system, cardiovascular system, and connective tissues. o Endoderm: Develops into the gastrointestinal tract, liver, pancreas, and lungs. 3. Embryonic Folding:  o The embryo folds along the cranial-caudal and lateral axes, initiating the body shape. Week 4: Pathologies Related to Embryonic Development 16. Potential Developmental Defects: o Anencephaly: Caused by failure of the cranial neuropore to close, resulting in a lethal defect. o Spina Bifida: Occurs when the caudal neuropore fails to close, affecting spinal cord development. If you have a lumbar non closure of the neuropore, all the nerves originating in that region are compromised and we will have of course a loss of funtion of the limbs. So, this depends on the region involving this lesion. o Sirenomelia (Mermaid Syndrome): A rare condition caused by insufficient mesoderm development, leading to fused lower limbs. o Sacrococcygeal Teratoma: A tumor from pluripotent cells in the Notochord if reabsorption fails, common in newborns. 17. Preventive Measures: o Folic Acid Supplementation is recommended for women of childbearing age, as it significantly reduces the risk of neural tube defects by approximately 70%. 18. End of Embryonic Period: o By the end of the fourth week, the basic structure of the embryo is established with primary organ primordia, marking the end of gastrulation.