Ventricular-subventricular Zone Fractones Are Speckled Basement Membranes That Function as a Neural Stem Cell Niche

Mol Biol Cell. 2019 Jan 1;30(1):56-68. doi: 10.1091/mbc.E18-05-0286. Epub 2018 Oct 31.

Abstract

Neural stem cells (NSCs) are retained in the adult ventricular-subventricular zone (V-SVZ), a specialized neurogenic niche with a unique cellular architecture. It currently remains unclear whether or how NSCs utilize basement membranes (BMs) in this niche. Here, we examine the molecular compositions and functions of BMs in the adult mouse V-SVZ. Whole-mount V-SVZ immunostaining revealed that fractones, which are fingerlike processes of extravascular BMs, are speckled BMs unconnected to the vasculature, and differ in their molecular composition from vascular BMs. Glial fibrillary acidic protein (GFAP)-positive astrocytes and NSCs produce and adhere to speckled BMs. Furthermore, Gfap-Cre-mediated Lamc1flox(E1605Q) knockin mice, in which integrin-binding activities of laminins are specifically nullified in GFAP-positive cells, exhibit a decreased number and size of speckled BMs and reduced in vitro neurosphere-forming activity. Our results reveal niche activities of fractones/speckled BMs for NSCs and provide molecular insights into how laminin-integrin interactions regulate NSCs in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Basement Membrane / blood supply
  • Basement Membrane / cytology
  • Basement Membrane / metabolism*
  • Cell Proliferation
  • Endothelial Cells / cytology
  • Endothelial Cells / metabolism
  • Ependyma / cytology
  • Ependyma / metabolism
  • Glial Fibrillary Acidic Protein / metabolism
  • Integrins / metabolism
  • Laminin / metabolism
  • Lateral Ventricles / cytology
  • Lateral Ventricles / metabolism*
  • Mice, Inbred C57BL
  • Mutation / genetics
  • Neural Stem Cells / cytology
  • Neural Stem Cells / metabolism*
  • Stem Cell Niche*

Substances

  • Glial Fibrillary Acidic Protein
  • Integrins
  • Laminin