The paucity of neurogenesis in the adult Central Nervous System (CNS) is not due to the lack of multipotential progenitor cells, but to the fact that only some regions of the adult CNS continue to express appropriate neurogenic cues. Although the relative contribution of cell-autonomous and extrinsic factors to cell fate decisions is not clear, a variety of studies have demonstrated that multipotential progenitor cells in the adult CNS respond to cues derived from the local environment. In vivo grafting experiments of immortalized, primary, or cultured progenitor cells have demonstrated that heterotopically injected neuronal precursors will migrate and differentiate according to their target site, revealing that local extrinsic signals can overcome cell autonomous mechanisms and re-direct regional specification. Most recently, experiments have shown that adult progenitor cells isolated from a non-neurogenic region will give rise to neurons when transplanted into a neurogenic region. These result make clear the importance of environmental factors produced by neurogenic zones.
My aim i s to begin to molecularly characterize these factors through manipulation of progenitor cells in an in vitro hippocampal slice assay. The advantage of this approach over current paradigms is that it will provide contextual information that cannot be derived from single cell clonal assays, while affording an ease of manipulation which is not possible in vivo.
