Induction of neurogenesis in nonconventional neurogenic regions of the adult central nervous system by niche astrocyte-produced signals

The central nervous system (CNS) of adult mammals regenerates poorly; in vivo, neurogenesis occurs only in two restricted areas, the hippocampal subgranular zone (SGZ) and the subventricular zone (SVZ). Neurogenic potential depends on both the intrinsic properties of neural progenitors and the environment, or niche, in which progenitor cells reside. Isolation of multipotent progenitor cells from broad CNS regions suggests that the neurogenic potential of the adult CNS is dictated by local environmental cues. Here, we report that astrocytes in the neurogenic brain regions, the SGZ and SVZ, of adult mice release molecular signals, such as sonic hedgehog (Shh), that stimulate adult neural progenitors to reenter the cell cycle and generate new neurons in vitro and in vivo. Transplantation of SGZ astrocytes or application of Shh caused de novo neurogenesis from the non-neurogenic neocortex of adult mice. These findings identify a molecular target that can activate the dormant neurogenic potential from nonconventional neurogenic regions of the adult CNS and suggest a novel mechanism of neural replacement therapy for treating neurodegenerative disease and injury without transplanting exogenous cells.