Steroid hormone signaling and the control of adult stem cell activity in Drosophila

Major challenges remain before clinical stem cell-based regenerative therapies for congenital birth defects and childhood diseases can be widely applied; for example, it is largely unknown how stem cells respond to the hormonal changes characteristic of pediatric growth. Due to their sensitivity to changes in organismal physiology, Drosophila germline stem cells (GSCs) are an excellent model system to investigate how hormonal cues are integrated with the intrinsic molecular mechanisms that regulate stem cell activity. GSCs directly respond to the steroid hormone ecdysone via the chromatin remodeling factor NURF and the transcription factor E74; however, it is unclear whether or how E74 may act in concert with NURF, or how E74 controls stem cell activity at the molecular level. We will utilize Drosophila genetic mutants and in vivo DNA binding assays to investigate how E74 is activated in GSCs, and identify the molecular targets of E74 that prevent GSC loss and stimulate the production of GSC progeny. Given the similarity between Drosophila and human steroid hormone signaling, our study will help clarify how stem cell activity is tethered to changes in the physiological environment, and provide new insight into the molecules critical for this response.

Scholars @ ECU