DIFFERENTIATION OF ADULT HIPPOCAMPUS-DERIVED PROGENITORS INTO OLFACTORY NEURONS IN-VIVO

NEUROGENESIS continues throughout adulthood in discrete regions. Proli ferative zones include the subependymal zone(1-4), from where progenit ors migrate along the rostral migratory pathway to differentiate into neurons in the olfactory bulb(4), and the hippocampal subgranular zone , where they migrate and differentiate into granule neurons(5-7). Prog enitors isolated from adult subependymal zone exhibit in vitro neuroge nesis when stimulated with epidermals(8,9) or fibroblast growth factor (10). Cultured adult rat hippocampal progenitors (AHPs) grafted to adu lt rat hippocampus show site specific neuronal differentiation(11). We re we investigate determinants of multipotentiality in the adult centr al nervous system, by grafting AHPs into homotypic (hippocampus) or he terotypic (the rostral migratory pathway) neurogenic sites or a hetero typic, non-neurogenic site (the cerebellum). We found that grafts into neurogenic, but not non-neurogenic sites, showed neuronal differentia tion. Furthermore, AHPs grafted in the rostral migratory pathway migra ted into the olfactory bulb, differentiating into tyrosine-hydroxylase -positive neurons, a non-hippocampus phenotype. These results reveal t hat AHP populations can respond to persistent neuronal differentiation cues in the adult central nervous system.