PROJECT SUMMARY/ABSTRACT Successful gamete production and survival of offspring in humans and invertebrates depends on optimal nutrition. The molecular mechanisms connecting gamete production with nutritional cues, however, remain unclear. Steroid hormones, via specific nuclear receptors, are diet-induced signals that promote germ cell development. Our long-term goal is to characterize how ovarian cells respond to steroid hormone signaling. Our undergraduate-powered research team uses the genetically tractable Drosophila ovary to monitor germ cell development in vivo in response to dietary and hormonal cues. The steroid hormone ecdysone has long been recognized for its role in oocyte development. Previous studies, however, have been unable to disentangle the multitude of effects of the steroid hormone, precluding identification of relevant molecular mechanisms. Our lab has developed novel reagents to specifically isolate germ cell autonomous reception of ecdysone signaling independent of its other roles. Building on our previous studies, our team of undergraduates and Master's students will test the hypothesis that ecdysone signaling through the receptor EcR autonomously in germ cells promotes an undifferentiated germ cell fate in germline stem cells, and follicle assembly in differentiated germ cells. In Aims 1 and 2, we will use sophisticated genetic tools, cell signaling reporters, and transcriptomics, and novel transcriptional enhancers to determine the transcriptional response to EcR in undifferentiated germ cells. In Aim 3, we will use gain and loss of function approaches combined with live cell imaging to test in vivo how EcR in germ cells promotes follicle formation. Results from these experiments will further our understanding of the molecular mechanisms by which steroid signaling promotes oocyte growth and survival, which have long been under-explored. Furthermore, this proposal will continue to support infrastructure at a large, regional, rural, public university, using a very approachable model system to provide high-impact biomedical research experiences to underserved undergraduates in a supportive training environment.

PROJECT NARRATIVE Maternal diet is critical for oocyte quality, rate of production, and offspring survival, yet the molecular mechanisms by which diet-induced hormones regulate oocyte development remain unclear. Using a powerful genetic model, this proposal will help elucidate how hormones influenced by maternal diet promote gamete production.