title: VCAM1 is essential to maintain the structure of the SVZ niche and acts as an environmental sensor to regulate SVZ lineage progression.
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.
authors.affiliation: Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
authors.forename: Erzsebet
authors.initials: E
authors.lastname: Kokovay
authors.forename: Yue
authors.initials: Y
authors.lastname: Wang
authors.forename: Gretchen
authors.initials: G
authors.lastname: Kusek
authors.forename: Rachel
authors.initials: R
authors.lastname: Wurster
authors.forename: Patty
authors.initials: P
authors.lastname: Lederman
authors.forename: Natalia
authors.initials: N
authors.lastname: Lowry
authors.forename: Qin
authors.initials: Q
authors.lastname: Shen
authors.forename: Sally
authors.initials: S
authors.lastname: Temple
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D002478:Cells, Cultured; D053583:Interleukin-1beta / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism*; D016548:Prosencephalon / Q000166:cytology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D055153:Stem Cell Niche / Q000502:physiology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*
chemical_list: D053583:Interleukin-1beta; D008562:Membrane Glycoproteins; D017382:Reactive Oxygen Species; D019010:Vascular Cell Adhesion Molecule-1; C488842:Cybb protein, mouse; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases