Hedgehog Controls Quiescence and Activation of Neural Stem Cells in the Adult Ventricular-Subventricular Zone

Stem Cell Reports. 2016 Oct 11;7(4):735-748. doi: 10.1016/j.stemcr.2016.08.016. Epub 2016 Sep 22.

Abstract

Identifying the mechanisms controlling quiescence and activation of neural stem cells (NSCs) is crucial for understanding brain repair. Here, we demonstrate that Hedgehog (Hh) signaling actively regulates different pools of quiescent and proliferative NSCs in the adult ventricular-subventricular zone (V-SVZ), one of the main brain neurogenic niches. Specific deletion of the Hh receptor Patched in NSCs during adulthood upregulated Hh signaling in quiescent NSCs, progressively leading to a large accumulation of these cells in the V-SVZ. The pool of non-neurogenic astrocytes was not modified, whereas the activated NSC pool increased after a short period, before progressively becoming exhausted. We also showed that Sonic Hedgehog regulates proliferation of activated NSCs in vivo and shortens both their G1 and S-G2/M phases in culture. These data demonstrate that Hh orchestrates the balance between quiescent and activated NSCs, with important implications for understanding adult neurogenesis under normal homeostatic conditions or during injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Cycle
  • Gene Deletion
  • Hedgehog Proteins / metabolism*
  • Lateral Ventricles / cytology*
  • Lateral Ventricles / metabolism*
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Neural Stem Cells / metabolism*
  • Neurogenesis
  • Neurons
  • Patched Receptors / genetics
  • Resting Phase, Cell Cycle*
  • Signal Transduction*
  • Stem Cell Niche

Substances

  • Hedgehog Proteins
  • Patched Receptors