Neural Crest Cells and Embryonic Development

Embryology L4-P1: The Embryonic Period

• The embryonic period is also known as the period of organogenesis
• It occurs from the third to eighth weeks of development
• During this time, each of the three germ layers (ectoderm, mesoderm, and endoderm) develops into specific tissues and organs
• By the end of the second month, the major features of the external body form are recognizable
• The majority of birth defects occur between the third and eighth weeks
• Environmental or genetic insults during this period can lead to spontaneous abortion, but not all cases result in loss
• Defects that occur between the third and eighth week are more likely to result in a viable fetus than when they occur earlier

Derivatives of the Ectodermal Germ Layer

• At the beginning of the third week, the ectodermal germ layer has a disc shape, broader cephalically than caudally
• The notochord and prechordal mesoderm induce the overlying ectoderm to thicken, forming the neural plate
• The neural plate cells become neuroectoderm
• This induction is the initial event in neurulation

Neurulation

• Neurulation is the process where the neural plate forms the neural tube
• The process is regulated by the planar cell polarity pathway
• Key events include lengthening of the neural plate and lateral-to-medial cell movement in the ectoderm and mesoderm planes
• Neural folds elevate to form neural folds
• Neural groove formation is a result of folding
• Neural folds fuse in the midline to form the neural tube
• Cephalic and caudal neuropores initially connect the neural tube to the amniotic cavity
• These neuropores close during the process (cranial closes at day 25; caudal closes at day 28)

Neural Crest Cells

• Cells on the lateral border/crest of the neuroectoderm detach from their neighbors
• The cells undergo an epithelial-to-mesenchymal transition to move into the underlying mesoderm
• A dorsal pathway might migrate through the dermis to cells in the ectoderm
• A ventral pathway might migrate through the anterior half of each somite to become various structures
• These cells are critically important in the formation of multiple tissues/organs and about one-third of birth defects and cancers

Embryonic Period - P2: Derivatives of the Mesodermal Germ Layer

• Initially, mesodermal cells form a thin sheet on either side of the midline
• By day 17, cells close to the midline proliferate, forming the thickened paraxial mesoderm
• Cells further out from the midline remain as thin lateral plate mesoderm
• Lateral plate mesoderm divides into somatic and splanchnic layers
• During differentiation, intercellular cavities form in the lateral plate and divide into layers
• Somatic (parietal) mesoderm lines the amnion
• Splanchnic (visceral) mesoderm covers the yolk sac
• The intraembryonic cavity is formed with the appearance of the layers
• Intermediate mesoderm connects paraxial and lateral mesoderm structures

Paraxial Mesoderm

• By the third week, paraxial mesoderm segments into somitomeres
• These segments first appear in the cephalic region and form in a head-to-tail manner
• Somitomeres are specialized mesodermal cells to differentiate into somites
• In the head region, somitomeres form in association with the segmentation of the neural plate and form mesenchyme
• Caudally, somitomeres form somites
• The first pair of somites arises in the occipital region and occurs by day 20 of development
• Approximately 3 pairs of somites arise per day until about 42 or 44 pairs (of various types) are present at the end of the fifth week

Somite Differentiation

• Somites form from presomitic mesoderm
• They exhibit a donut shape
• Somite cells undergo epithelization with a thin lumen
• Ventral and medial cells lose characteristics of epithelial cells to become mesenchymal cells
• Collectively, these form the sclerotome, differentiating into vertebrae and ribs
• Dorsomedial and ventrolateral edges differentiate into precursors for muscle cells, whereas the area between forms the dermatome
• Muscle precursors become mesenchymal to migrate under the dermatome to form the dermomyotome

Intermediate Mesoderm

• Intermediate mesoderm temporarily connects paraxial and lateral plate mesoderm
• It forms urogenital structures (including the nephrogenic cord and the gonads, for the kidneys and reproductive organs)
• Forms from segmental cell clusters or an unsegmented structure
• Cervical and thoracic regions form segmental cell clusters
• Caudally, the intermediate mesoderm forms an unsegmented mass known as the nephrogenic cord

Lateral Plate Mesoderm

• Splits into parietal (somatic) and visceral (splanchnic) layers
• These layers line the intraembryonic cavity and surround organs
• Parietal layer with overlying ectoderm forms the body wall folds
• The parietal layer forms the dermis, bones, connective tissue of the limbs, and sternum
• Cells of the parietal layer migrate to form costal cartilages, limb, and body wall muscles
• Visceral layer plus embryonic endoderm form the gut tube
• Mesoderm cells from the parietal layer secrete fluid to form membranes along the cavity surfaces

Blood and Blood Vessels

• Blood cells and blood vessels originate from mesoderm
• Vasculogenesis is the formation of blood vessels; it also begins from an existing vessel system
• Blood islands first appear in the yolk sac and lateral plate mesoderm around 3 weeks of gestation
• Hemangioblasts are a precursor to blood and vessel formation
• Definitive hematopoietic stem cells develop from the aorta-gonad-mesonephros (AGM) region, near the mesonephric kidney
• Liver becomes the major hematopoietic organ from weeks 2 to 7

Derivatives of the Endodermal Germ Layer

• Endoderm forms the epithelial and parenchymal regions of gastrointestinal organs
• The endoderm originally covers the ventral surface of the embryo and forms the roof of the yolk sac
• Growth of the brain vesicles makes the embryo bulge into the amniotic cavity and takes a fetal position
• Two lateral folds close to enclose the ventral body wall
• The gut tube forms three regions: foregut, hindgut, and midgut
• The midgut connects to the yolk sac by the vitelline duct
• The foregut connects to the oropharyngeal membrane
• The hindgut connects to the cloacal membrane
• Various derivatives result from the interactions of those structures

External Appearance during the Second Month

• By the fourth week, the main external features are visible, including somites and pharyngeal arches
• The age of the embryo is typically given in terms of somites, but later, is described via crown-rump length (CRL) measured in millimeters
• The second month marks increased growth in the head, limb formation, and the development of facial features, ears, eyes, nose, etc