Fractones: Home and Conductors of the Neural Stem Cell Niche

Abstract

Throughout life, neural stem cells proliferate and differentiate in restricted zones of the brain, termed niches, to produce new neurons and glial cells. In these niches, growth factors and extracellular matrix (ECM) molecules determine the fate of neural stem and progenitor cells (NSPC). However, the precise compounds and the mechanisms that regulate growth factors and other signaling molecules in the niches are unknown. Based on the evidence that NSPCs proliferate next to blood vessels in the dentate gyrus, the concept of a vascular niche for neurogenesis has been initially proposed. In the subventricular zone of the lateral ventricle, the most neurogenic zone in adulthood, we have found that NSPC directly contact a novel type of ECM structure that we have named fractones. Fractones contain heparan sulfate proteoglycans (HSPG) that collect and concentrate the neurogenic growth factor FGF2 at the NSPC surface and likely direct its signaling via tyrosine kinase receptors. Our preliminary results indicate that FGF2 binding to fractone-HSPG is essential for activating FGF2 at the NSPC surface. Moreover, we have found fractones express diverse HSPG at the surface of proliferating NSPC during development, even before the brain vasculature emerges. Therefore, fractones hold considerable promise for promoting growth factors at the stem cell surface to ultimately regulate neurogenesis during development and adulthood.