Affiliations: 1) University of Virginia; 2) Shepherd University
Keywords: c. neural stem cells; o. stem cells
Drosophila neural stem cells (NSC), known as neuroblasts (NB), undergo asymmetric cell division throughout development in order to make the adult fly brain. Dietary nutrients provide essential building blocks necessary for NB growth and proliferation. However, there is a subset of NBs, known as mushroom body neuroblasts (MB NBs), which are able to continue proliferation regardless of extrinsic dietary nutrient availability. My research aims to understand the molecular mechanism regulating nutrient-independent MB NBs proliferation. Transcriptional co-activator Yorkie (Yki) is well known for its role in maintaining tissue growth and size. However, it remains unclear whether Yki controls the nutrient-independent proliferation of the MB NBs. Upon NB specific Yki knockdown, MB NBs stopped proliferation in response to dietary nutrient withdrawal and resumed proliferation upon re-feeding. Upon expression of a constitutively active form of Yki, all NBs in the fly brain continued cell proliferation independent of dietary nutrient availability. This suggest that Yki regulates NB proliferation decision in response to nutrient availability. Yki requires a DNA binding partner for its function and Sd is the most well-known in Drosophila. I knocked down Sd in a NB specific manner and it did not stop MB NBs from proliferating in a nutrient-independent manner which suggests that Sd might not be the Yki binding partner in the brain. NB specific knockdown and over-expression of Myc resulted in a similar phenotype as Yki. I will conduct two experiments to determine whether there is a genetic interaction between Myc and Yki in the MB NBs. I will over-express Myc in Yki knockdown NBs, and also over-express Yki in Myc knockdown NBs.