Gamete production in mammals and insects is controlled by cell signaling pathways that facilitate communication between germ cells and somatic cells. Nuclear receptor signaling is a key mediator of many aspects of reproduction, including gametogenesis. For example, the NR5A sub-family of nuclear receptors are essential for gonad development and sex steroid production in mammals. Despite the original identification of the NR5A sub-family in the model insect Drosophila melanogaster, it has been unclear whether Drosophila NR5A receptors directly control oocyte production. Ftz-f1 is expressed throughout the ovary, including in germline stem cells, germline cysts, and several populations of somatic cells. We demonstrate that ftz-f1 is required in follicle cells prior to stage 10 to promote egg chamber survival at the mid-oogenesis checkpoint. Our data suggest that egg chamber death in the absence of ftz-f1 is due, at least in part, to failure of follicle cells to exit the mitotic cell cycle or failure to accumulate oocyte-specific factors in the germline. Taken together, these results demonstrate that, as in mammals, the NR5A sub-family promotes maximal reproductive output in Drosophila. Our data underscore the importance of nuclear receptors in the control of reproduction and highlight the utility of Drosophila oogenesis as a key model for unraveling the complexity of nuclear receptor signaling in gametogenesis.

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