VCAM1 is essential to maintain the structure of the SVZ niche and acts as an environmental sensor to regulate SVZ lineage progression

Cell Stem Cell. 2012 Aug 3;11(2):220-30. doi: 10.1016/j.stem.2012.06.016.

Abstract

Neurons arise in the adult forebrain subventricular zone (SVZ) from Type B neural stem cells (NSCs), raising considerable interest in the molecules that maintain this life-long neurogenic niche. Type B cells are anchored by specialized apical endfeet in the center of a pinwheel of ependymal cells. Here we show that the apical endfeet express high levels of the adhesion and signaling molecule vascular cell adhesion molecule-1 (VCAM1). Disruption of VCAM1 in vivo causes loss of the pinwheels, disrupted SVZ cytoarchitecture, proliferation and depletion of the normally quiescent apical Type B cells, and increased neurogenesis in the olfactory bulb, demonstrating a key role in niche structure and function. We show that VCAM1 signals via NOX2 production of reactive oxygen species (ROS) to maintain NSCs. VCAM1 on Type B cells is increased by IL-1β, demonstrating that it can act as an environmental sensor, responding to chemokines involved in tissue repair.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Adhesion
  • Cells, Cultured
  • Interleukin-1beta / metabolism
  • Membrane Glycoproteins / metabolism
  • Mice
  • Mice, Transgenic
  • NADPH Oxidase 2
  • NADPH Oxidases / metabolism
  • Neural Stem Cells / cytology*
  • Neural Stem Cells / metabolism*
  • Prosencephalon / cytology*
  • Reactive Oxygen Species / metabolism
  • Signal Transduction
  • Stem Cell Niche / physiology*
  • Vascular Cell Adhesion Molecule-1 / metabolism*

Substances

  • Interleukin-1beta
  • Membrane Glycoproteins
  • Reactive Oxygen Species
  • Vascular Cell Adhesion Molecule-1
  • Cybb protein, mouse
  • NADPH Oxidase 2
  • NADPH Oxidases