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. In this proposal, a team of undergraduates and Master?s students will test the hypothesis that ecdysone signaling directly modulates the cell cycle in germ cell daughters to promote oocyte specification.
In Aim 1, we will use candidate and unbiased approaches to define how ecdysone signaling promotes germ cell mitotic divisions.
In Aim 2, we will use new germline-specific tools to genetically manipulate ecdysone signaling and investigate whether ecdysone signals promote germ cell mitotic divisions and/or meiotic onset independently of somatic cell signaling.
In Aim 3, we will query the roles of germ cell-enriched ecdysone signaling targets as possible mechanisms driving oocyte specification. Our study will conclusively demonstrate whether and how ecdysone signaling promotes germ cell proliferation and oocyte differentiation via multiple, parallel mechanisms. 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 first- generation and minority undergraduates in a supportive training environment.
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.
|Blake, Amelia J; Finger, Danielle S; Hardy, Victoria L et al. (2017) RNAi-Based Techniques for the Analysis of Gene Function in Drosophila Germline Stem Cells. Methods Mol Biol 1622:161-184|
|Ables, Elizabeth T; Drummond-Barbosa, Daniela (2017) Steroid Hormones and the Physiological Regulation of Tissue-Resident Stem Cells: Lessons from the Drosophila Ovary. Curr Stem Cell Rep 3:9-18|