VCAM1 Is Essential to Maintain the Structure of the SVZ Niche and Acts as an Environmental Sensor to Regulate SVZ Lineage Progression

SummaryNeurons 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.

Graphical AbstractFigure optionsDownload high-quality image (239 K)Download as PowerPoint slideHighlights
► Neural stem cells (NSCs) are anchored in the ependymal niche by VCAM1 on their endfeet
► Blocking VCAM1 activates quiescent NSCs to undergo proliferation and neurogenesis
► VCAM1 activates NOX2 to generate the level of ROS needed for NSC maintenance
► VCAM1 acts as an environmental NSC sensor, responding to humoral factors like IL-1β