Home NEUR 310 Tuesday, January 14, 2014

Tuesday, January 14, 2014 CC-BY-NC
Developmental Neurobiology part 2

Maintainer: admin

1Differentiation of neural precursor cells

  • We used drosophila to learn this
  • proneural genes (achaete-scute transcription factors) are expressed in potential neuroblast
  • neural fate involves delta-notch signaling,
    • can be random (neuroblast formation)
    • or predetermined (assymmetric distribution of Numb)

1.1Delta Notch signaling

  • lateral inhibition : one cell becomes neuroblast and the surrounding others become suppporting cells

    • Mechanism: Delta-notch signaling
      • Delta binds Notch
      • Notch's intracellular domain gets cleaved
      • the cleaved part enters the nucleus and activates genes that block proneural transcription factors of bHLH (basic helix loop helix)
    • Notch function is required in cells that become epidermis
    • slight imbalance in Notch signaling develops due to increased Delta expression
    • low Notch signaling in cells -> neuroblasts
    • mutation of Notch or Delta cause overproduction of neuroblasts

  • Delta-notch also controls neural differentiation in vertebrate's CNS

    • inhibition of Notch --> increased number of neurons
    • via neurogenin , a bHLH, which prootes neural differentiation

  • Numb controls neural fate

    • asymmetricaly localized in dividing progenitor cells
    • binds to cytosolic tail of Notch
    • in Drosophila, each external sensory organs arise from a single SOP (sensory organ precurosr)
      • sensory bristles of Drosophila are composed of 4 cells from SOP
      • asymetric division of Numb allows this to happen

1.2Neuraonl and Glial cell fates

  • CNS
    • PDGF maintains proliferation of oligodendrocyte progenitor cells
    • CNTF: promote astrocytes
  • PNS
    • neural crest cells migrate from dorsal part of neural tube to periphery
    • they then encounter signals which determine their fates
    • BMP : impose neuronal identity
    • GGF: secreted by sympathetic neurons, promote glial fate

2Neuronal Migration

  • PNS: migrate to periphery and undergo differentiation

  • CNS: differentiate in ventricular zone and migrate to different layers of the brain

    • migration: inside-out neurogenesis. cells born early are in the deepest layer
    • deciding factors of cell fate
      • phenotype of cell is specified during / before the last S phase
      • vertical cleavage: two similar daughter cells that reenter the cell cycle
      • horizontal cleavage: asymmetric division, apical daughter cells migrates

    • deciding factors of migration

      • neurons migrate along radial glia cells
      • regulation of movement
        • BDNF and NTF: envrionmental factors, motogenic factor
        • Lis : regulate mitotubule
      • regulation of adhesion
        • Astn1 (astrotactin): favor adhesion to glia
        • Reelin: in extracellular matrix, regulate layer formation
          • secreted by some neurons such as Cajal-Retzius cells
          • receptors: VLDLR and ApoER2
          • binding of Reelin lead to tyrosine phosphorylation of intracellular adaptor Dab1

    • lissencephaly: migration arrest of neurons before reaching their targets

      • reeler mouse: mutation in Reelin, tremors and ataxia and disruption of laminar structure in the brain
      • scrambler mouse: mutation in Dab1 disruption in lamination
        • reduces the speed of migration of neurons and ability to detach from the radial glia