Control of cell division in the adult brain by heparan sulfates in fractones and vascular basement membranes

Abstract

Regulation of cell division in adult tissues and organs requires the coordination of growth factors at the surface of potentially-dividing cells in specific anatomic loci named germinal niches. However, the biological components and physiological system that control growth factors in the germinal niches are unknown. In the adult brain, no function has been attributed to fractones, the fractal-shaped extracellular matrix structures located in the subventricular zone (SVZ) next to neural stem and progenitor cells. Here, we show that BMP-7 (bone morphogenetic protein-7) and FGF-2 (fibroblast growth factor-2) modulate cell division in the SVZ only if the growth factors bind to heparan sulfates localized in fractones and adjoined vascular basement membranes. Our results strongly suggest that fractones and specialized basement membranes function as stem cell niche structures, capturing and potentiating growth factors to regulate cell division in the adult brain.