Regulation of Neurogenesis by Jagged1 in the Embryonic SVZ

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DESCRIPTION (provided by applicant): The goal of this proposal is to investigate the role of Jagged1 during late embryonic neurogenesis in the subventricular zone (SVZ) of the olfactory system. Prior studies have shown that loss of Jagged1 leads to reduced cell division within the SVZ. However, what cell-types are affected within the SVZ to produce this phenotype is still unknown. In the SVZ, neural stem cells give rise to transit amplifying cells, which in turn produce neuroblast precursors. I hypothesize that Jagged1 is required for one or both of these transitions during neurogenesis. I will use Jagged1 mutants and immunohistochemical approaches to determine what cell types are affected during neurogenesis. Jagged1 is known to regulate cells division in the SVZ. However, what mechanisms control Jagged1 activation and expression? It has been shown that Jagged1 is activated by wnt signaling in cancer cells. Wnt is also known to regulate neurogenesis in the brain, but how this process occurs is still poorly understood. I hypothesize that wnt regulates neurogenesis by controlling Jagged1 expression in the SVZ. I will use SVZ-derived neurospheres and pharmacological approaches to determine if Jagged1 mediates wnt regulation of neurogenesis. PUBLIC HEALTH RELEVANCE: Neurogenesis in the subventricular zone plays a critical role in olfactory learning and memory. In the SVZ, neurogenesis increases under conditions that are triggered by ischemia and stroke. Therefore, understanding the mechanisms that regulate neurogenesis in the SVZ is an important process for many health implications.