Perlecan is required for FGF-2 signaling in the neural stem cell niche

Stem Cell Res. 2014 Mar;12(2):492-505. doi: 10.1016/j.scr.2013.12.009. Epub 2013 Dec 28.

Abstract

In the adult subventricular zone (neurogenic niche), neural stem cells double-positive for two markers of subsets of neural stem cells in the adult central nervous system, glial fibrillary acidic protein and CD133, lie in proximity to fractones and to blood vessel basement membranes, which contain the heparan sulfate proteoglycan perlecan. Here, we demonstrate that perlecan deficiency reduces the number of both GFAP/CD133-positive neural stem cells in the subventricular zone and new neurons integrating into the olfactory bulb. We also show that FGF-2 treatment induces the expression of cyclin D2 through the activation of the Akt and Erk1/2 pathways and promotes neurosphere formation in vitro. However, in the absence of perlecan, FGF-2 fails to promote neurosphere formation. These results suggest that perlecan is a component of the neurogenic niche that regulates FGF-2 signaling and acts by promoting neural stem cell self-renewal and neurogenesis.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / physiology
  • Cell Growth Processes / physiology
  • Fibroblast Growth Factor 2 / pharmacology*
  • Heparan Sulfate Proteoglycans / deficiency
  • Heparan Sulfate Proteoglycans / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Neural Stem Cells / cytology
  • Neural Stem Cells / metabolism*
  • Neurogenesis / physiology
  • Neurons / cytology
  • Neurons / drug effects
  • Neurons / metabolism*
  • Signal Transduction
  • Stem Cell Niche / drug effects
  • Stem Cell Niche / physiology*

Substances

  • Heparan Sulfate Proteoglycans
  • Fibroblast Growth Factor 2
  • perlecan