Dual roles of Notch in regulation of apically restricted mitosis and apicobasal polarity of neuroepithelial cells

Neuron. 2011 Jan 27;69(2):215-30. doi: 10.1016/j.neuron.2010.12.026.

Abstract

How the mitosis of neuroepithelial stem cells is restricted to the apical ventricular area remains unclear. In zebrafish, the mosaic eyes(rw306) (moe/epb41l5(rw306)) mutation disrupts the interaction between the putative adaptor protein Moe and the apicobasal polarity regulator Crumbs (Crb), and impairs the maintenance of neuroepithelial apicobasal polarity. While Crb interacts directly with Notch and inhibits its activity, Moe reverses this inhibition. In the moe(rw306) hindbrain, Notch activity is significantly reduced, and the number of cells that proliferate basally away from the apical area is increased. Surprisingly, activation of Notch in the moe(rw306) mutant rescues not only the basally localized proliferation but also the aberrant neuroepithelial apicobasal polarity. We present evidence that the Crb⋅Moe complex and Notch play key roles in a positive feedback loop to maintain the apicobasal polarity and the apical-high basal-low gradient of Notch activity in neuroepithelial cells, both of which are essential for their apically restricted mitosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Cell Movement / physiology
  • Cell Polarity / physiology*
  • Embryonic Development / physiology
  • Eye Proteins / genetics
  • Eye Proteins / metabolism*
  • Glycogen Synthase Kinase 3 / metabolism
  • Glycogen Synthase Kinase 3 beta
  • Mitosis / physiology*
  • Motor Neurons / cytology
  • Motor Neurons / physiology
  • Mutation
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Neuroepithelial Cells* / cytology
  • Neuroepithelial Cells* / physiology
  • Proto-Oncogene Proteins c-akt / metabolism
  • Receptors, Notch / genetics
  • Receptors, Notch / metabolism*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Stem Cells / cytology
  • Stem Cells / physiology
  • Zebrafish / anatomy & histology
  • Zebrafish / physiology
  • Zebrafish Proteins / genetics
  • Zebrafish Proteins / metabolism*

Substances

  • Crb1 protein, zebrafish
  • Eye Proteins
  • Nerve Tissue Proteins
  • Receptors, Notch
  • Recombinant Fusion Proteins
  • Zebrafish Proteins
  • epb41l5 protein, zebrafish
  • Glycogen Synthase Kinase 3 beta
  • Proto-Oncogene Proteins c-akt
  • Glycogen Synthase Kinase 3