RE

Chapter 15. Neural Tube

Neural Tube: Birth of the Central Nervous System

Development of the Ectoderm

  • BMP Levels and Ectoderm Fate
    • Bone Morphogenetic Proteins (BMP) regulate ectoderm development.
    • Low BMP levels: Ectoderm differentiates into the neural tube.
    • Presence of BMP Inhibitors: Critical for neural tube formation.

Neurulation

  • Definition of Neurulation: The process of forming the neural tube, crucial for central nervous system development.
  • Cell Movement and Shape Change: Understanding how cells rearrange to create the neural structures.

Types of Neurulation

  • Primary Neurulation:
    • The neural plate rolls up to form a tube.
  • Secondary Neurulation:
    • Involves the formation of a solid mass of tissue that hollows out to create the neural tube.
    • In mammals, starts at the sacral vertebrae region.

Neural Plate Formation

  • The neural plate forms through signaling from the dorsal mesoderm, transforming ectoderm into columnar cells, forming a raised structure.
  • Can include up to 50% of the ectoderm in its formation.

Tissue Shape Changes in Neurulation

  • The neural plate becomes longer and narrower due to convergent extension, where cells move closer together.
  • Cells also preferentially divide in the anterior-posterior direction rather than sideways, facilitating extension.

Neural Plate Bending

  • Medial Hinge Point (MHP):
    • Cells at the midline form MHP, which gets induced by the notochord to take a wedge shape.
  • Dorsolateral Hinge Points:
    • Found on either side, also forming wedge shapes, contributing to the tube formation by bending the neural plate.
  • The surface ectoderm applies pressure on the neural plate, aiding in bending through sideways cell division.

Neural Tube Closure

  • Neural Folds:
    • They meet and adhere, leading to the formation of the neural tube.
    • Cells at the edges form neural crest, which migrates to create peripheral neurons and other cell types.
  • Regulation by Cadherins:
    • Cells express E-cadherin initially.
    • During neurulation, they begin to express N-cadherin to help separate neural tube from surface ectoderm, allowing neural crest cells to not express either cadherin.

Defects in Neural Tube Closure

  • Approximately 1 in 1000 live births experience neural tube defects.
  • Spina Bifida:
    • Defect in posterior neural tube closure; may result in vertebrae not fusing or spinal cord bulging.
  • Anencephaly:
    • Defect in anterior neural tube closure leading to underdeveloped forebrain and skull.
  • Folic Acid's Role:
    • Folic acid deficiency correlated with neural tube defects; promotes proper DNA methylation.
    • Supplements recommended for women of child-bearing age.

Cell-Cell Signaling: Dorsal-Ventral Differences

  • Dorsal vs. Ventral:
    • Dorsal side: Sensory neurons.
    • Ventral side: Motor neurons.
  • Signaling Molecules:
    • BMP and TGF-β from ectoderm above, Sonic Hedgehog (Shh) from notochord below induce differentiation in the neural tube.

Gradient Formation

  • TGF-β and Shh Gradients:
    • Induction occurrences shaped by the notochord; TGF-β signals induce the dorsal region, while Shh induces the ventral region of the neural tube.

Consequences of Shh Expression

  • Shh signaling suppresses Pax6 expression, important for eye formation.
  • Abnormal Shh levels may cause defects, potentially resulting in cyclopia (one eye formation).