Contribution of Extracellular Matrix Component Landscapes in the Adult Subventricular Zone to the Positioning of Neural Stem/Progenitor Cells

Abstract

Neurogenesis persists in restricted regions of the adult brain, including the subventricular zone (SVZ). Adult neural stem cells (NSCs) in the SVZ proliferate and give rise to new neurons and glial cells depending on intrinsic and environmental cues. Among the multiple factors that contribute to the chemical, physical, and mechanical components of the neurogenic niche, we focused on the composition of the extracellular matrix (ECM) of vasculature and fractones in the SVZ. The SVZ consists of ECM-rich blood vessels and fractones during development and adulthood, and adult neural stem/progenitor cells (NS/PCs) preferentially attach to the laminin-rich basal lamina. To examine the ECM preference of adult NS/PCs, we designed a competition assay using cell micropatterning. Although both laminin and collagen type IV, which are the main components of basal lamina, act as physical scaffolds, adult NS/PCs preferred to adhere to laminin over collagen type IV. Interestingly, the ECM preference of adult NS/ PCs could be manipulated by chemokines such as stromal-derived factor 1 (SDF1) and alpha 6 integrin. As SDF1 re-routes NSCs and their progenitors toward the injury site after brain damage, these results suggest that the alteration in ECM preferences may provide a molecular basis for context dependent NS/PC positioning.