Neural stem cells have the capacity to generate vast numbers of neuronal progeny over long periods of time when cultured in vitro, yet during normal development this mitotic potential must be kept in check so that each region of the central nervous system contains the appropriate number of neurons and glia. As neural stem cells have the remarkable capacity of regenerating the damaged brain, understanding the developmental regulation of their divisions may have important implications for future stem cell-based therapies. The remodelling of the Drosophila central nervous system (CNS) from its larval to adult form provides a genetically tractable system for studying region-specific proliferation at the level of individual neural stem cells, termed neuroblasts. Using in vivo clonal analysis, our lab recently explored the nature of the stop mechanism limiting how many times a postembryonic neuroblast (pNB) can divide. These studies have identified a pathway linking a conserved family of positional information genes, the Hox genes, to the developmental time at which neural proliferation ceases. The purpose of my project is to conduct a genome-wide mosaic screen to identify new genes that are also involved in regulating neural stem cell divisions.
This will take advantage of several genetic tools and particular strains of Drosophila that have been developed in the host laboratory recently. New stem cell division genes will be characterised at the genetic and molecular level and their vertebrate orthologues studied in the context of hindbrain development.
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