Steroid hormone-induced wingless ligands tune female intestinal size in Drosophila

Abstract

Abstract Female reproduction comes at great expense to energy metabolism compensated by extensive organ adaptations including intestinal size. Upon mating, Drosophila ovaries release the steroid hormone Ecdysone that stimulates a 30% net increase of absorptive epithelium by intestinal stem cell (ISC) divisions. Here, we uncover the transcription factor crooked legs (crol) as intraepithelial coordinator of Ecdysone-induced ISC mitosis by establishing Rapport, the first spatiotemporally-controlled dual expression and tracing system for the analysis of paracrine effects on ISC behaviour. Rapport tracing revealed that Ecdysone-induced Crol controls mitogenic Wnt/wg-ligand release from epithelial enterocytes towards ISC, which is counterbalanced by Crol-repression of string/CDC25 and Cyclin-B directly in ISC. Rapport-based ISC tumours confirm paracrine stimulation through the Ecdysone-Crol-Wg axis on mitotic behaviour. Finally, mathematical modelling corroborates increasing enterocyte numbers and Wnt/wg-degradation to set a stable post-mating intestinal size. Together, our findings provide insights into complex endocrine growth control mechanisms during mating-induced adaptations and gastrointestinal cancer.