RESEARCH ARTICLE Nuclear receptor Ftz-f1 promotes follicle maturation and ovulation partly via bHLH/PAS transcription factor Sim Elizabeth M Knapp1, Wei Li1, Vijender Singh2, Jianjun Sun1,2* 1Department of Physiology & Neurobiology, University of Connecticut, Storrs, United States; 2Institute for Systems Genomics, University of Connecticut, Storrs, United States Abstract The NR5A-family nuclear receptors are highly conserved and function within the somatic follicle cells of the ovary to regulate folliculogenesis and ovulation in mammals; however, their roles in Drosophila ovaries are largely unknown. Here, we discover that Ftz-f1, one of the NR5A nuclear receptors in Drosophila, is transiently induced in follicle cells in late stages of oogenesis via ecdysteroid signaling. Genetic disruption of Ftz-f1 expression prevents follicle cell differentiation into the final maturation stage, which leads to anovulation. In addition, we demonstrate that the bHLH/PAS transcription factor Single-minded (Sim) acts as a direct target of Ftz-f1 to promote follicle cell differentiation/maturation and that Ftz-f1’s role in regulating Sim expression and follicle cell differentiation can be replaced by its mouse homolog steroidogenic factor 1 (mSF-1). Our work provides new insight into the regulation of follicle maturation in Drosophila and the conserved role of NR5A nuclear receptors in regulating folliculogenesis and ovulation. Introduction *For correspondence:
[email protected] Female fertility, an essential half of the reproductive equation, requires proper follicle maturation and ovulation. The NR5A family of nuclear receptors are critical for the success of these complex Competing interests: The ovarian processes across species (Jeyasuria et al., 2004; Meinsohn et al., 2019; Mlynarczuk et al., authors declare that no 2013; Sun and Spradling, 2013; Suresh and Medhamurthy, 2012).