Peptidergic signaling from clock neurons regulates reproductive dormancy in Drosophila melanogaster

• Published in: PLoS genetics Vol. 15; no. 6; p. e1008158
• Main Authors: Nagy, Dóra, Cusumano, Paola, Andreatta, Gabriele, Anduaga, Ane Martin, Hermann-Luibl, Christiane, Reinhard, Nils, Gesto, João, Wegener, Christian, Mazzotta, Gabriella, Rosato, Ezio, Kyriacou, Charalambos P, Helfrich-Förster, Charlotte, Costa, Rodolfo
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 13.06.2019; Public Library of Science (PLoS)
• Subjects: Animals; Animals, Genetically Modified - genetics; Biology; Biology and Life Sciences; Brain - metabolism; Calcium; Cellular signal transduction; Circadian rhythm; Circadian Rhythm - genetics; CLOCK Proteins - genetics; Cyclic adenosine monophosphate; Cyclic AMP; Developmental stages; Diapause; Diapause - genetics; Diapause - physiology; Dormancy; Drosophila; Drosophila melanogaster; Drosophila melanogaster - genetics; Drosophila melanogaster - growth & development; Drosophila Proteins - genetics; Explants; Gene expression; Gene Expression Regulation - genetics; Genetic aspects; Genetic engineering; Genetic regulation; Genetic research; Genetics; Genomes; Hormones; Insects; Insulin; Insulin - genetics; Medicine and Health Sciences; Nervous system; Neurobiology; Neurons; Neurons - metabolism; Neuropeptide F; Neuropeptides; Neuropeptides - genetics; Neurosciences; Peptides; Physiological aspects; Proteins; Reproduction - genetics; Research and Analysis Methods; Signal Transduction - genetics; Supervision; Zoological research; Italy; United Kingdom > UK; Germany
• ISSN: 1553-7404; 1553-7390; 1553-7404
• DOI: 10.1371/journal.pgen.1008158

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.