The bHLH-PAS transcriptional complex Sim:Tgo plays active roles in late oogenesis to promote follicle maturation and ovulation

Across species, ovulation is a process induced by a myriad of signaling cascades that ultimately results in activation of proteolytic enzymes and degradation of the follicle wall to release encapsulated oocytes. Follicles need to first mature and gain ovulatory competency before ovulation. However, the signaling pathways regulating follicle maturation are incompletely understood in Drosophila and other species. Our previous work showed that bHLH-PAS transcription factor Single-minded (Sim) likely plays important roles for follicle maturation downstream of the NR5A-family nuclear receptor Ftz-f1 in Drosophila. Here, we explore the mechanism of Sim-regulated follicle maturation. We demonstrate that Tango (Tgo), another bHLH-PAS protein acts as a cofactor of Sim to promote follicle cell differentiation from stages 10 to 12. In addition, we discovered that re-upregulation of Sim in stage-14 follicle cells is also essential to promote ovulatory competency by upregulating octopamine receptor in mushroom body (OAMB), matrix metalloproteinase 2 (Mmp2), and NADPH oxidase (NOX), either independent of or in conjunction with the zinc-finger protein Hindsight (Hnt). All of these factors are critical for successful ovulation. Together, our work indicates that the transcriptional complex Sim:Tgo plays multiple roles in late-stage follicle cells to promote follicle maturation and ovulation.