TY - JOUR A1 - Nagy, Dóra A1 - Cusumano, Paola A1 - Andreatta, Gabriele A1 - Martin Anduaga, Ane A1 - Hermann-Luibl, Christiane A1 - Reinhard, Nils A1 - Gesto, João A1 - Wegener, Christian A1 - Mazzotta, Gabriella A1 - Rosato, Ezio A1 - Kyriacou, Charalambos P. A1 - Helfrich-Förster, Charlotte A1 - Costa, Rodolfo T1 - Peptidergic signaling from clock neurons regulates reproductive dormancy in Drosophila melanogaster JF - PLoS Genetics N2 - With the approach of winter, many insects switch to an alternative protective developmental program called diapause. Drosophila melanogaster females overwinter as adults by inducing a reproductive arrest that is characterized by inhibition of ovarian development at previtellogenic stages. The insulin producing cells (IPCs) are key regulators of this process, since they produce and release insulin-like peptides that act as diapause-antagonizing hormones. Here we show that in D. melanogaster two neuropeptides, Pigment Dispersing Factor (PDF) and short Neuropeptide F (sNPF) inhibit reproductive arrest, likely through modulation of the IPCs. In particular, genetic manipulations of the PDF-expressing neurons, which include the sNPF-producing small ventral Lateral Neurons (s-LNvs), modulated the levels of reproductive dormancy, suggesting the involvement of both neuropeptides. We expressed a genetically encoded cAMP sensor in the IPCs and challenged brain explants with synthetic PDF and sNPF. Bath applications of both neuropeptides increased cAMP levels in the IPCs, even more so when they were applied together, suggesting a synergistic effect. Bath application of sNPF additionally increased Ca2+ levels in the IPCs. Our results indicate that PDF and sNPF inhibit reproductive dormancy by maintaining the IPCs in an active state. Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-231681 VL - 15 ER -