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。SVZ在整个发育和成年期产生新的神经元，这些神经元在一定程度上负责嗅觉球细胞结构的终身阐述和完善。这些新的神经元从SVZ迁移到嗅球通过称为吻侧迁移流的途径。然而，引导这些迁移细胞到嗅球的分子机制还不清楚。在强有力的初步调查结果的基础上 涉及ephrinB和EphB蛋白在控制吻侧迁移的细胞内的迁移 蒸汽，我们已经建立了新型的测定系统，使我们能够开始定义星形胶质细胞在成人迁移中的确切作用。我们提出了三个具体的目标：确定ephrin-B2在星形胶质细胞鞘中的表达是否限制了成体神经前体细胞在吻侧迁移流中的迁移。确定EphB 2是否需要星形胶质细胞依赖性迁移的成体神经祖细胞在吻迁移流。确定是否星形胶质细胞内衬吻迁移蒸汽限制迁移EphB 2在迁移神经祖细胞的激活。由于以前的结果已经证明祖细胞增殖减少抑郁症和EphB和ephrinB的表达是改变神经元活动的变化，我们提出的研究将有董事会的影响，祖细胞迁移的基础生物学和细胞分子机制控制的病理生理学的理解。

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.