Ecdysone signaling promotes expression of multifunctional RNA binding proteins essential for ovarian germline stem cell self-renewal in Drosophila

Abstract

ABSTRACTSteroid hormones promote stem cell self-renewal in many tissues; however, the molecular mechanisms by which hormone signaling is integrated with niche-derived signals are largely uncharacterized. In the Drosophila ovary, the steroid hormone ecdysone promotes germline stem cell (GSC) self-renewal. Despite strong evidence that ecdysone modulates the reception of bone morphogenetic protein (BMP) signals in GSCs, transcriptional targets of ecdysone signaling that facilitate BMP reception are unknown. Here, we report that ecdysone signaling promotes the expression of the heterogeneous nuclear ribonucleoproteins (hnRNPs) squid, hephaestus, Hrb27C, and Hrb87F in GSCs. These hnRNPs functionally interact with ecdysone signaling to control GSC number and are cell autonomously required in GSCs for their maintenance. We demonstrate that hnRNPs promote GSC self-renewal by binding to transcripts essential for proper BMP signaling, including the BMP receptors thickveins and punt. Our findings support the model that stem cells coordinate local and long-range signals at the transcriptional and post-transcriptional levels to maintain self-renewal in response to physiological demand.GRAPHICAL ABSTRACTEcdysone signaling regulates distinct hnRNPs that bind to BMP signaling targets to control GSC self-renewal.SUMMARY STATEMENTEcdysone signaling promotes expression of heterogeneous ribonucleoproteins that modulate BMP-dependent germline stem cell self-renewal in the Drosophila ovary.