ECTODERM

• Key maternal factors of an amphibian blastula showing a subset of the genetic interactions involved in germ layer formation:

  1. Fox Family Genes
  2. Runx2
  3. Oct4/Pou5f1
  4. Hnf4
  5. VegT
  6. Wnt/β-cat
• Between 3.5 and 4.5 dpc, the embryo, now known as a blastocyst, consists of two cell populations: An outer multipotent trophectoderm (TE) (expressing Cdx2), and a mosaic inner pluripotent inner cell mass (ICM) population.

  
• Label the human gastrula

  A) Oropharyngeal Membrane

  B) Notochord

  C) Node

  D) Primitive Streak

  E) Amnion

  F) Cloacal Membrane

  G) Neural Plate

  H) Amnion

  I) Primitive Streak

  J) Neural Fold

  K) Neural Groove

  L) Somites

  M) Neurenteric Canal

  N) Node

  O) Primitive Streak

  
• The TE differentiates into cells that constitute the placenta including the extraembryonic endoderm (EXE)
• Hypoblast cells that remain in close contact with the epiblast differentiate into visceral endoderm (VE) while those that migrate along the basement membrane of the TE form the tPA+ parietal endoderm (PaE), resulting in the formation of the yolk sac. 
• The derivatives of the ectoderm

  1. Surface ectoderm
  2. Neural crest
  3. Neural tube
• What is the process of the development of ectodermal organs?

  1. Epithelial Placode
  2. Bud
  3. Morphogenesis
  4. Adult Organ
• Placode as a basal unit of ectodermal organogenesis
• Neurulation is the formation of the vertebrate nervous system in embryos.
• During gastrulation, a population of the dorsal ectoderm is specified to become neural ectoderm
• The signals involved in neurulation are noggin, chordin, and follistatin
• Neural plate will be induced to form a hollow neural tube = spinal cord, brain, etc.
• What morphogenetic movement is at work here?

  Convergence

  
• What are the 2 mechanisms involved in the formation of the neural tube?

  1. Primary Neurulation
  2. Secondary Neurulation
• Primary Neurulation – Cells that flank neural plate induce the neural plate to proliferate, invaginate, pinch off to form neural tube
• Secondary Neurulation – Mesenchyme cells of the ectoderm coalesce to form a solid cord
• DLHP - dorsolateral hinge point

  MHP - median hinge point

  NC - notochord

  NE - neuroepithelium

  NNE - nonneural ectoderm

  PM - paraxial mesoderm
• Primary Neurulation occurs in a rostro-caudal (anterior-posterior) direction
• Neurulation in different vertebrates varies across species, both with regard to the number of closure points, their timing and the order in which these points close
• Multiple closure points - at the hindbrain/cervical boundary, at the forebrain/midbrain boundary and at the most rostral end of the forebrain.
• Two points of closure initiation - at the level of the future midbrain and at the hindbrain-cervical boundary, with bidirectional zippering between the sites.
• Xenopus embryos exhibit closure almost simultaneously along the entire body axis
• In teleost fish there is no formation of neural folds at all; rather, the NP cells coalesce to form a neural keel and the NT lumen opens subsequently within this structure
• Neural tube separates from surrounding ectoderm and seals to form hollow tube

  • Mediated by expression of adhesion molecules
  • N-cadherin is expressed in neural plate
  • E-cadherin is expressed in remaining ectoderm
• If N-cadherin is over-expressed in the surrounding surface ectoderm, neural tube closure is impeded
• Neural tube closure is caused by the coordination among nuclear genes, cytoplasmic proteins and ECM proteins
• Spina Bifida – a defect where posterior neural tube does not fuse; Spinal cord remains exposed
• Anencephaly – a defect where anterior neural tube does not fuse; Forebrain ceases to develop; Lethal
• Neural tube must maintain dorsal-ventral polarity

  • Sensory neurons - dorsal
  • Motor neurons- ventral
• Neural Crest Cells (NCCs) - Originate in dorsal neural tube and migrate extensively to populate the body with a variety of cell types
• Neural crest cells form at the junction of the neural plate and the epidermal ectoderm
• FoxD3

  • If inhibited, no neural crest cells form
  • Necessary for neural crest specification
• Slug

  • If inhibited, neural crest cells cannot migrate
  • Necessary for neural crest migration
• Ventral pathway

  • cells move through anterior portion of somite toward ventral side of embryo
  • Cells become: sensory neurons, sympathetic ganglia, medulla of adrenal gland
• Dorsolateral pathway

  • Cells move between epidermis and somite
  • Cells become: melanocytes
• The sacral NCC migrates ventrally and colonizes the gut after the vagal crest
• Issues that arise during the formation and migration of neural crest cells are known as neurocristopathies, with varying effects depending on the location of the dysfunction.
• What are the classifications of neurocristopathies (NCPs)?

  1. Dysgenetic NCPs
  2. Neoplastic NCPs
  3. Mixed dysgenetic and neoplastic NCPs
• Treacher Collins Syndrome - a prototypic facial dysostosis and NCP of cranial neural crest origin.
• The formation and patterning during neurulation

  1. neural plate
  2. elevation
  3. folding
  4. convergence, closure, and patterning