Molecular mechanisms of oocyte development in Drosophila

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.

Grant Number: 2R15GM117502-03
NIH Institute/Center: NIH
Principal Investigator: Elizabeth Ables