A Genome Wide Association Study Implicates Oseg2 and Bicra in Neural Stem Cell Reactivation

During early life neurogenesis, neural stem cells divide to give rise to the thousands of morphologically and functionally diverse neurons that will build an adult brain. During this time, neural stem cells progress through periods of quiescence and proliferation, with the transition from quiescence to proliferation referred to as reactivation. Reactivation is of broad interest in the field of stem cell biology and neurodevelopment, as proper timing of reactivation is required for the production of a functioning adult brain, and disruptions to reactivation can cause a wide variety of neurodevelopmental disorders. Previous research has provided a wealth of knowledge about the way that neural stem cells function, however the majority of these studies have not accounted for genetic variation. The work presented in Chapter 1 of this dissertation revealed that Drosophila melanogaster show genetic variation in how stem cells progress through development, specifically in neural stem cell reactivation. Identifying genetic variation in a well-studied phenotype such as reactivation offered the opportunity to conduct a forward genetic screen as a means to identify new genes that had not been previously implicated in reactivation. We conducted a genome wide association study on percent reactivation at 24 hours after larval hatching (ALH) using 152 lines from the Drosophila Genetic Reference Panel. Our work revealed significant genetic variation in percent reactivation at 24hr ALH and implicated Outer Segment 2 (Oseg2) and BRD4 interacting chromatin remodeling complex associated protein (Bicra) as two new genes of interest that are involved in neural stem cell reactivation.