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In  Drosophila melanogaster  eight 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 of  dilp8 /DILP8 and  Lgr3  in adult female flies and the functional role of DILP8 signaling. The only site where we found both  dilp8  expression and DILP8 immunolabeling was in follicle cells around mature eggs.  Lgr3  expression 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 in  dilp8  mutants as well as after  dilp8 -RNAi using  dilp8  and 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 to  Lgr3  expressing follicle cells as well as systemically to  Lgr3  expressing 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 of  dilp8  expression 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.

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