Glial Control of Neuronal Progenitor Cell Migration

描述(申请人提供)：起源于脑室下区(SVZ)的神经前体细胞整合到神经回路中，介导嗅觉学习并影响习惯形成。SVZ在整个发育和成年期都会产生新的神经元，这在一定程度上对Olfactor球状细胞结构的终生细化和完善负有责任。这些新的神经元通过一条被称为吻端迁移流的通路从SVZ迁移到嗅球。然而，引导这些迁移细胞到嗅球的分子机制还不是很清楚。以强有力的初步调查结果为基础 EphB和EphB蛋白在嘴移行细胞迁移控制中的作用 STEAM，我们已经建立了新的检测系统，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。我们提出了三个特定的目标：确定星形胶质细胞鞘中EPhin-B2的表达是否限制了成体神经前体细胞在吻端迁移蒸汽中的迁移。确定EphB2是否是成体神经前体细胞在吻端迁移过程中星形胶质细胞依赖迁移所必需的。确定排列在吻端迁移蒸汽中的星形胶质细胞是否通过激活迁移的神经前体细胞中的EphB2来限制迁移。由于先前的结果表明抑郁症时祖细胞的增殖减少，并且EphB和EphinB的表达因神经元活动的改变而改变，我们提出的研究将对理解祖细胞迁移的基本生物学和控制病理生理的细胞-分子机制产生重大影响。

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.