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Regulation of neurogenesis by interkinetic nuclear migration through an apical-basal notch gradient.

The different cell types in the central nervous system develop from a common pool of progenitor cells. The nuclei of progenitors move between the apical and basal surfaces of the neuroepithelium in phase with their cell cycle, a process termed interkinetic nuclear migration (INM). In the retina of zebrafish mikre oko (mok) mutants, in which the motor protein Dynactin-1 is disrupted, interkinetic nuclei migrate more rapidly and deeply to the basal side and more slowly to the apical side. We found that Notch signaling is predominantly activated on the apical side in both mutants and wild-type. Mutant progenitors are, thus, less exposed to Notch and exit the cell cycle prematurely. This leads to an overproduction of early-born retinal ganglion cells (RGCs) at the expense of later-born interneurons and glia. Our data indicate that the function of INM is to balance the exposure of progenitor nuclei to neurogenic versus proliferative signals.

Pubmed ID: 18805097

Authors

  • Del Bene F
  • Wehman AM
  • Link BA
  • Baier H

Journal

Cell

Publication Data

September 19, 2008

Associated Grants

  • Agency: NEI NIH HHS, Id: EY012406
  • Agency: NEI NIH HHS, Id: EY013855
  • Agency: NEI NIH HHS, Id: EY01467
  • Agency: NEI NIH HHS, Id: R01 EY012406
  • Agency: NEI NIH HHS, Id: R01 EY012406-05
  • Agency: NEI NIH HHS, Id: R01 EY012406-09
  • Agency: NEI NIH HHS, Id: R01 EY013855
  • Agency: NEI NIH HHS, Id: R01 EY013855-04
  • Agency: NEI NIH HHS, Id: R01 EY013855-06
  • Agency: NINDS NIH HHS, Id: R01 NS053358
  • Agency: NINDS NIH HHS, Id: R01 NS053358-02

Mesh Terms

  • Animals
  • Body Patterning
  • Cell Cycle
  • Cell Differentiation
  • Cell Nucleus
  • Embryo, Nonmammalian
  • Gene Expression Regulation, Developmental
  • Microtubule-Associated Proteins
  • Mutation
  • Neuroepithelial Cells
  • Organogenesis
  • Receptors, Notch
  • Retina
  • Retinal Ganglion Cells
  • Stem Cells
  • Zebrafish
  • Zebrafish Proteins