Glial Control of Neuronal Progenitor Cell Migration

描述（由申请人提供）：起源于脑室下区（SVZ）的神经祖细胞整合到介导嗅觉学习和影响习惯形成的神经回路中。在整个发育和成年期间，SVZ产生新的神经元，这在一定程度上负责嗅球细胞结构的终身完善和完善。这些新的神经元通过一个叫做吻侧迁移流的途径从SVZ迁移到嗅球。然而，引导这些迁移细胞到嗅球的分子机制尚不清楚。以强有力的初步调查结果为基础

DESCRIPTION (provided by applicant): Neural progenitor cells originating in the subventricular zone (SVZ) integrate into the neural circuitry that mediates olfactory learning and impacts habit formation. The SVZ produces new neurons throughout development and adulthood that are in part responsible for the life-long elaboration and refinement of the olfactor bulb cytoarchitecture. These new neurons migrate from the SVZ to the olfactory bulb via a pathway called the rostral migratory stream. However, the molecular mechanisms that guide these migrating cells to the olfactory bulb are poorly defined. Building on strong initial findings implicating ephrinB and EphB proteins in control of migration of cells within the rostral migratory steam, we have established novel assay systems that allow us to begin to define the exact role of astrocytes in adult migration. We propose three specific aims: Determine whether expression of ephrin-B2 in the astrocyte sheath constrains migration of adult neural progenitor cells within the rostral migratory steam. Determine whether EphB2 is required for astrocyte dependent-migration of adult neural progenitor cells in the rostral migratory steam. Determine whether astrocytes lining the rostral migratory steam constrain migration by activation of EphB2 in migrating neural progenitor cells. Because previous results have demonstrated progenitor cell proliferation is reduced in depression and EphB and ephrinB expression is altered by changes in neuronal activity our proposed studies will have board impact on the understanding of the basic biology of progenitor cell migration and the cellular-molecular mechanisms controlling pathophysiology.