Cell migration and differentiation in the olfactory bulb

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DESCRIPTION (provided by applicant): Neural stem cells in the subventricular zone (SVZ) are involved in the continual generation of new cells throughout development and in adult. The major target of these newly formed cells is the olfactory bulb. These SVZ progenitors migrate from the SVZ along the rostral migratory stream and into the olfactory bulb. In the olfactory bulb these cells migrate radially to different layers and differentiate into primarily interneurons, although glia are also thought to be generated. The cues directing the differentiation of these cells, and many of the mechanisms involved in their radial migration in the olfactory bulb, are unclear. This goal of this research is to investigate the migration and differentiation of SVZ progenitors in the olfactory bulb. Aim 1 will determine what cell phenotypes are derived from SVZ progenitor migration at different developmental stages, and whether the fate of these cells can be perturbed by environmental cues using organotypic slice culture. Aim 2 investigates the mechanisms used by SVZ progenitors to migrate along the rostral migratory stream and into the olfactory bulb. These experiments focus upon the relationship between migrating neurons and different putative migratory scaffolds present in postnatal and adult, and the role that matrix metalloproteinases may have in facilitating the migration of these cells. Understand the mechanisms of SVZ progenitor migration through the olfactory bulb and cues governing phenotype selection have important implications for the use of these cells as clinical therapy.