Thursday, January 9, 2014

Developmental Neurobiology part 1

1Early development¶

• Egg fertilization
• Cleavages to form Blastula, (mitotic division -> Blastula is a hollow ball of cells
• Gastrulation :
  • forming multi-layer: ectoderm, mesoderm, and endoderm
  • rostral-caudal and dorsal-ventral axes are defined
• Neurulation
  • neural plate forms, bends, elevates, and fuses to form a tube
    • internal neural tube: CNS
    • external epidermis
    • neural crest cells: CNS
  • birth defect: spinal bifida when neurla tube doesn't close
• Formation of brain and spinal cord
  • rostral-caudal and dorsal-ventral axes
  • neuroepithelial cells become neurons or glia

2Neural induction¶

• region interacting with another region and influences its fate or behaviour
• "The Organizer Region" : dorsal lip of blastopore
  • can induce "dorsalization" of the ventral region of an embryo

• dorsal midline mesoderm induces overlying ectoderm to become neural plate ectoderm

• neural fate is default:

  • dissociated ectodermal cells give rise to neural cells
  • inhibiting BMP signaling leads to neural fate
    • BMP-4 : induces ectodermal cells to become epidermal
    • BMP4 is expressed in animal cap cells at the beginning of gastrula and disappears later in the neural plate
  • other secreted molecules isolated from dorsal lip (which induce neural cell fate)
    • Noggin:
      • rescue UV-induced ventralization (i.e. not dorsalization : have neural tube)
      • expressed in dorsal mesoderm and in the organizer
    • Chordin
      • can induce a second neural tube in ventral blastomeres
      • expresses in blastopore the organizer during gastrulation
    • Follistatin
      • expressed in blastopore the organizer during gastrulation
  • these organizer-derived induces promote neural fate by antagonizes the BMP signaling via binding BMP
    • so the organizer has its effect by inhibiting BMP signaling, not directly inducing neural fate

2.1Rostral-caudal Axis¶

• rostral structure (brain): induced by Chordin, Noggin, and Follistatin
• caudal tissues (spinal cord): induced by FGFS, retinoic acids
• segmentation : Hox genes
  • expressed in hindbrain and spinal cord
  • segmented structures induced by combinations of hox genes (Hox code)
  • regulated by intrinsic mechanism of the neural tube and signals from mesodermal cells

2.2Dorsal-ventral Axis¶

• dorsal of spinal cord: process sensory input
  • signal : Dorsalin and BMPs
  • BMP: induces differentiation of cells into dorsal interneurons, expressed by roofplate cells, activates Smad transcription factors
  • dorsalin: inhibit differentiation of motorneurons
• ventral of spinal cord: motor output
  • signal : sonic hedgehog (SHH)
  • normal signaling : PTC receptor inhibits SMO
  • SHH binds to PTC to stop inhibition, SMO activates transcription factor Gli