DrosophilaInsulin-Like Peptide 8 (DILP8) in Ovarian Follicle Cells Regulates Ovulation and Metabolism

InDrosophila melanogastereight insulin-like peptides (DILP1-8) are encoded on separate genes. These DILPs are characterized by unique spatial and temporal expression patterns during the lifecycle. Whereas, functions of several of the DILPs have been extensively investigated at different developmental stages, the role of DILP8 signaling is primarily known from larvae and pupae where it couples organ growth and developmental transitions. In adult female flies, a study showed that a specific set of neurons that express the DILP8 receptor, Lgr3, is involved in regulation of reproductive behavior. Here, we further investigated the expression ofdilp8/DILP8 andLgr3in adult female flies and the functional role of DILP8 signaling. The only site where we found bothdilp8expression and DILP8 immunolabeling was in follicle cells around mature eggs.Lgr3expression was detected in numerous neurons in the brain and ventral nerve cord, a small set of peripheral neurons innervating the abdominal heart, as well as in a set of follicle cells close to the oviduct. Ovulation was affected indilp8mutants as well as afterdilp8-RNAi usingdilp8and follicle cell Gal4 drivers. More eggs were retained in the ovaries and fewer were laid, indicating that DILP8 is important for ovulation. Our data suggest that DILP8 signals locally toLgr3expressing follicle cells as well as systemically toLgr3expressing efferent neurons in abdominal ganglia that innervate oviduct muscle. Thus, DILP8 may act at two targets to regulate ovulation: follicle cell rupture and oviduct contractions. Furthermore, we could show that manipulations ofdilp8expression affect starvation resistance suggesting effects on metabolism. Possibly this reflects a feedback signaling between ovaries and the CNS that ensures nutrients for ovary development. In summary, it seems that DILP8 signaling in regulation of reproduction is an ancient function, conserved in relaxin signaling in mammals.