The long term goal of this research project is to understand how nutrient derived cues integrate with cell intrinsic programs to control timing and rate of neurogenesis. All neurons within our brains are generated from the asymmetric cell divisions of neural stem cells, which are self- renewing multi-potent progenitors. Neural stem cells play a key role in regulating brain size and neuronal diversity, as this population remains actively engaged in the cell cycle throughout development. While much effort has been geared towards identifying genes and the cell signaling pathways that regulate neural stem cell self-renewal, less is known about how extrinsic factors, local and systemic, integrate with intrinsic neural stem cell factors to control timing and rate of neurogenesis. Here, using the Drosophila brain as a genetically tractable model system, we investigate how nutrient derived extrinsic signals integrate with cell intrinsic programs to control timing and rate of neurogenesis. In this proposal, we will investigate (1) whether the machinery that drives asymmetric cell division itself also play a role in regulating neural stem cell growth and proliferation, (2) how nutrition regulates neural stem cell proliferation, and (3) how a particular transcription factor, which is highly conserved, can override nutrient-dependent requirements for neural stem cell proliferation.
Results from the proposed research could provide: 1) a better understanding of the basis of congenital birth defects, such as anencephaly or microcephaly and 2) insight into devising better methods for treatment of age-related cognitive decline in the elderly.
|Sipe, Conor W; Siegrist, Sarah E (2017) Eyeless uncouples mushroom body neuroblast proliferation from dietary amino acids in Drosophila. Elife 6:|