Differentiation of adult hippocampus-derived progenitors into olfactory neurons in vivo

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Abstract
NEUROGENESIS continues throughout adulthood in discrete regions. Proliferative zones include the subependymal zone1–4, from where progenitors migrate along the rostral migratory pathway to differentiate into neurons in the olfactory bulb4, and the hippocampal subgranular zone, where they migrate and differentiate into granule neurons5–7. Progenitors isolated from adult subependymal zone exhibit in vitro neurogenesis when stimulated with epidermal8,9 or fibroblast growth factor10. Cultured adult rat hippocampal progenitors (AHPs) grafted to adult rat hippocampus show site-specific neuronal differentiation11. Here we investigate determinants of multipotentiality in the adult central nervous system, by grafting AHPs into homotypic (hippocampus) or heterotypic (the rostral migratory pathway) neurogenic sites or a heterotypic, non-neurogenic site (the cerebellum). We found that grafts into neurogenic, but not non-neurogenic sites, showed neuronal differentiation. Furthermore, AHPs grafted in the rostral migratory pathway migrated into the olfactory bulb, differentiating into tyrosine-hydroxylase-positive neurons, a non-hippocampus phenotype. These results reveal that AHP populations can respond to persistent neuronal differentiation cues in the adult central nervous system.