Commemorative Lecture
نویسنده
چکیده
In the neurogenic niche of the adult mammalian brain, self-renewing neural stem cells (NSCs) give rise to committed neuronal progenitors within the subgranular zone (SGZ) of the dentate gyrus (DG).1 Astrocytes are an essential cell population that defines the SGZ niche, and astrocyte-derived factors have instructive effects that promote adult neurogenesis.2, 3 Recently, we showed that Wnt3 expression persists in the adult hippocampus and that Wnt3 is released by astrocytes to regulate adult neurogenesis in vitro and in vivo.4 In the canonical Wnt/β -catenin pathway, TCF transcription factors transduce Wnt/β-catenin signals to activate downstream target genes.49 However, the target gene(s) of Wnt/β-catenin signaling responsible for promoting adult neurogenesis have not been identified. Moreover, the regulatory mechanism underlying Wnt-mediated neuronal differentiation has not yet been elucidated. NeuroD1 is a proneural bHLH transcription factor essential for the development of the central nervous system (CNS), in particular the generation of granule cells in the hippocampus and cerebellum.10, 11 Environmental signals regulate adult neurogenesis at least in part through the activation of NeuroD1.12, 13 In preliminary studies, we showed that overexpression of NeuroD1 was sufficient to promote neuronal differentiation in adult hippocampal neural progenitors,14 whereas deletion of NeuroD1 resulted in decreased survival and maturation of newborn neurons.15 Thus, we hypothesized that astrocyte-derived Wnt signals might directly or indirectly regulate the transcription of NeuroD1 to control the transition of NSCs to committed neuronal progenitors. The HMG-box transcription factor Sox2 is expressed in embryonic stem cells and most uncommitted cells in the developing CNS.1618 Sox2, which can be detected Molecular and Cellular Mechanisms Contributing to the Regulation, Proliferation and Differentiation of Neural Stem Cells in the Adult Dentate Gyrus
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تاریخ انتشار 2010