Thursday, January 9, 2014 CC-BY-NC
Developmental Neurobiology part 1

Maintainer: admin

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