Germ cell division and encapsulation by somatic cells during Drosophila oogenesis require the orphan nuclear receptor ftz-f1

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 gonadogenesis and sex steroid production in mammals. Yet 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. Here, we demonstrate that ftz-f1 (NR5A3) is necessary for multiple aspects of early oocyte development. Ftz-f1 is expressed throughout the ovary, including in germline stem cells (GSCs), germline cysts, and several populations of somatic cells. Ftz-f1 is necessary in GSCs and their dividing daughters for timely mitotic cyst divisions and accumulation of oocyte-specific proteins in the presumptive oocyte which dictate oocyte positioning within the cyst. In parallel, ftz-f1 in somatic escort cells and pre-follicle cells promotes proper cyst division and cyst encapsulation. Interestingly, our data suggest that ftz-f1 promotes escort cell-dependent cyst encapsulation via a complex genetic interaction with the steroid hormone ecdysone. We propose the model that Ftz-f1 and ecdysone signaling via the Ecdysone Receptor (NR1H1) interdependently promote communication between escort cells and germ cells. Taken together, these results demonstrate that the reproductive functions of the NR5A sub-family are largely conserved between insects and mammals. 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.