Establishing new roles of Daughterless in the Drosophila melanogaster central nervous system. Mitchell D'Rozario¹, Tina Hu¹, Mohammad Nayal¹, Kaveesh Kutty¹, Daniel Marenda^1,2. 1) Department of Biology, Drexel University, Philadelphia, PA; 2) Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA.

   Proper neurodevelopment in all animals depends on basic helix-loop-helix (bHLH) proneural transcription factors that regulate how an undifferentiated cell develops into a neural precursor cell. TCF4, a vertebrates type I bHLH proneural protein has been linked to several neuropsychiatric diseases such as Pitt-Hopkins Syndrome (a disease characterized by severe mental and motor retardation) and schizophrenia.Daughterless (da), the only type I bHLH in flies, is an ubiquitously expressed protein with an established function in sex determination, differentiation of mesoderm, and as a proneural gene for establishing the central and peripheral nervous system. Consistent with its role as a transcription factor, Da has been previously localized in the nucleus of multiple cells in the CNS; however, we show that Da is also localized outside the nucleus within the axons of multiple neurons. We also have evidence that Da functions to regulate axonal development in post-mitotic cells, a novel function for this proneural bHLH factor. We suggest that the analysis of daughtlerss in post-mitotic neurons can complement and expand upon the existing studies for this disease, allowing a better understanding of the novel role of Daughterless in post-neurogenesis, neural development and TCF4 in Pitt-Hopkins Syndrome pathogenesis.