Neuregulins in Adult Neurogenesis and Migration

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DESCRIPTION (provided by applicant): In this project, we propose to study the role of one isoform of the receptor tyrosine kinases, ErbB4, and its ligands, the neuregulins (NRGs), in adult neurogenesis and migration of cells that form the rostral migratory stream (RMS). In adult mice, neural progenitor cells born in the anterior region of the lateral ventricle (SVZ) migrate as chains of neurons in the RMS to the olfactory bulb where they differentiate into interneurons. The ErbB4 receptor is prominently expressed in the RMS while all isoforms of NRGs are expressed in olfactory and cortical structures in the immediate surroundings of the RMS. In vitro, NRG-1 appears to block the formation of chains of migrating neurons and disperses chains that have already formed. NRG-2, on the other hand, induces neurogenesis in vitro and in vivo, suggesting that it recruits proliferative mechanisms. Here we propose to elucidate the role of the ErbB4 receptor in neurogenesis and migration of cells in the SVZ and RMS by infusing recombanant NRG's in the anterior ventricles of adult mice. We then propose to characterize the cell types affected by ErbB4 activation in the SVZ and RMS of adult mice. Finally, we propose to identify potential changes in rate, organization, and orientation of migrating neuroblasts in the RMS in response to ErbB4 activation and inactivation using real-time imaging as well as fixed tissue analyses. Through these efforts, we hope to gain an improved understanding of molecular mechanisms that regulate neural progenitor cell proliferation, migration and differentiation in the adult brain