Gαs regulates asymmetric cell division of cortical progenitors by controlling Numb mediated Notch signaling suppression

Neurosci Lett. 2015 Jun 15:597:97-103. doi: 10.1016/j.neulet.2015.04.034. Epub 2015 Apr 24.

Abstract

Asymmetric cell division, which plays fundamental roles in generating cell diversity during development, requires elaborate interactions between extrinsic cues and intrinsic cues. However, the precise nature of this type of interaction and its involving signaling mechanisms are poorly understood. Here, we demonstrate that Gαs is present in the proliferative region of ventricular zone in mouse developing neocortex and co-localizes with intrinsic cell fate determinant protein Numb in dividing apical progenitors. Targeted ablation of Gαs subunit in the cortical progenitor causes an alteration from asymmetric to symmetric cell division, consequently leading to increased progenitor proliferation. Mechanistically, we show that Gαs deletion significantly reduces Numb expression and activates notch signaling. Therefore, these results reveal a novel role of Gαs in control of neural progenitor asymmetric cell division via suppressing Numb mediated Notch signaling inhibition.

Keywords: Asymmetric cell division; Gα subunit; Neurogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Division
  • Cell Proliferation
  • Cerebral Cortex / cytology
  • Cerebral Cortex / embryology
  • Cerebral Cortex / metabolism*
  • Chromogranins
  • GTP-Binding Protein alpha Subunits, Gs / metabolism*
  • Membrane Proteins / metabolism*
  • Mice
  • Neocortex / cytology
  • Neocortex / embryology
  • Neocortex / metabolism*
  • Nerve Tissue Proteins / metabolism*
  • Neural Stem Cells / cytology
  • Neural Stem Cells / metabolism*
  • Receptors, Notch / metabolism*
  • Signal Transduction

Substances

  • Chromogranins
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Numb protein, mouse
  • Receptors, Notch
  • Gnas protein, mouse
  • GTP-Binding Protein alpha Subunits, Gs