NR5A family member ftz-f1 is necessary to promote oocyte development

Abstract

Gamete production in mammals and insects is intimately tied to nutrition status. Conversion of nutritionally-dependent physiological signals to molecular mechanisms underlying control of oogenesis, however, remains largely uncharacterized. Nuclear receptors (NRs) link physiological status to a cellular transcriptional response and are important mediators of reproduction, physiology, and tissue homeostasis. For example, mammalian NR5 family members SF-1 and LRH-1 are essential for gonadogenesis and sex steroid production. Two NR5 family members are encoded in the Drosophila genome: Hr39, which is necessary for female reproductive tract development, and ftz-f1, whose role in oogenesis has not been explored. Given that Hr39 is not intrinsically required for oogenesis, we hypothesized that ftz-f1 may fill a conserved NR role in Drosophila. ftz-f1 is expressed throughout the ovary, including in germline stem cells (GSCs), germline cysts, and several populations of somatic cells. Using Flippase/Flippase Recognition Target (Flp/FRT) mediated clonal analysis we analyzed the effects of loss of ftz-f1 function in germ and somatic cells throughout oogenesis. Germline-specific knockdown of ftz-f1 resulted in fewer GSCs as female flies aged. GSCs harboring two copies of the null ftz-f1ex7 mutation were more frequently displaced from the niche, as compared to controls. Loss of GSCs was not the result of alterations in cell cycle progression, adhesion, or accumulation of DNA damage. Loss of ftz-f1 was, however, correlated with the accumulation of GSC progeny (cystoblasts and two cell cysts) and delayed mitotic cyst divisions. We also observe that accumulation of the oocyte-specific RNA binding protein, Orb, is delayed in ftz-f1ex7 germline cysts; however, it is unclear whether this effect is independent of delayed cyst divisions. Taken together, our results suggest that ftz-f1 functions autonomously in dividing germ cells to promote germline development. Further, reduced ftz-f1 function in ovarian somatic cells resulted in enlarged egg chambers containing more than one 16-cell cyst, gaps in the follicular epithelium, and premature follicle death, suggesting impaired follicle encapsulation. Interestingly, egg chambers with mutant ftz-f1ex7 or ftz-f119 follicle cells often contained mis-positioned oocytes and/or decreased expression of oocyte specific markers. We conclude that ftz-f1 also functions specifically in differentiating follicle cells to promote oocyte fate and positioning. Our data add to a growing body of literature underscoring the importance of nuclear receptors in the control of reproduction.