Neuroepithelial progenitors undergo LGN-dependent planar divisions to maintain self-renewability during mammalian neurogenesis

Nat Cell Biol. 2008 Jan;10(1):93-101. doi: 10.1038/ncb1673. Epub 2007 Dec 16.

Abstract

During mammalian development, neuroepithelial cells function as mitotic progenitors, which self-renew and generate neurons. Although spindle orientation is important for such polarized cells to undergo symmetric or asymmetric divisions, its role in mammalian neurogenesis remains unclear. Here we show that control of spindle orientation is essential in maintaining the population of neuroepithelial cells, but dispensable for the decision to either proliferate or differentiate. Knocking out LGN, (the G protein regulator), randomized the orientation of normally planar neuroepithelial divisions. The resultant loss of the apical membrane from daughter cells frequently converted them into abnormally localized progenitors without affecting neuronal production rate. Furthermore, overexpression of Inscuteable to induce vertical neuroepithelial divisions shifted the fate of daughter cells. Our results suggest that planar mitosis ensures the self-renewal of neuroepithelial progenitors by one daughter inheriting both apical and basal compartments during neurogenesis.

MeSH terms

  • Animals
  • Brain / embryology
  • Brain / metabolism
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Cycle / physiology
  • Cell Cycle Proteins
  • Cell Differentiation
  • Cell Polarity
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Immunohistochemistry
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mitosis / genetics
  • Mitosis / physiology
  • Neuroepithelial Cells / cytology
  • Neuroepithelial Cells / metabolism*
  • Signal Transduction
  • Spindle Apparatus / physiology*
  • Stem Cells / cytology
  • Stem Cells / metabolism*

Substances

  • Carrier Proteins
  • Cell Cycle Proteins
  • LGN protein, mouse
  • Green Fluorescent Proteins