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

ECU Author/Contributor (non-ECU co-authors, if there are any, appear on document)

Samantha I McDonald (Creator)

Institution

East Carolina University (ECU )

Web Site: http://www.ecu.edu/lib/

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.

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Thesis

Language: English

Date: 2019

Keywords

ftz-f1, follicle cells, nuclear receptor

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