Abstract

A characteristic feature of all stem cell systems in long-lived metazoans is their capacity to produce stem cells and cells that are committed to terminal differentiation in a continuous way. Capacity for self-renewal endows stem cell populations with regenerative potential but also underlies susceptibility to neoplastic transformation. The adult brain subependymal zone (SEZ) is a very active neurogenic niche in which a relatively quiescent population of radial glia/astrocyte-like GFAP + neural stem cells (NSC) continually produce new neurons and oligodendrocytes, via a population of rapidly-diving transit-amplifying progenitor cells. Stem cell expansion in response to increased cellular demand suggests that niche signals can modulate division mode, but very little is known about the molecular players involved. Therefore, one approach to the understanding of self-renewal is to analyze the mechanisms that regulate the maintenance of normal NSCs in their natural environment. Although some intrinsic determinants are known to regulate stem cell division, the observation that stem cells can respond to excessive cellular demand in pathological situations or after traumatic injury suggests that they have ways to increase their number in response to external signals. Within the specialized microenvironments in which stem cells reside, vascular elements appear to play an important role in the regulation of stem cell self-renewal vs. commitment, both under normal and pathological conditions but the signalling pathways involved are still under investigation. I will present our most recent data on intrinsic and extrinsic regulators of NSC maintenance and homing.