PT - JOURNAL ARTICLE AU - Cynthia M. Chai AU - Mahdi Torkashvand AU - Maedeh Seyedolmohadesin AU - Heenam Park AU - Vivek Venkatachalam AU - Paul W. Sternberg TI - Interneuron Control of <em>C. elegans</em> Developmental Decision-making AID - 10.1101/2021.11.07.467589 DP - 2021 Jan 01 TA - bioRxiv PG - 2021.11.07.467589 4099 - http://biorxiv.org/content/early/2021/11/08/2021.11.07.467589.short 4100 - http://biorxiv.org/content/early/2021/11/08/2021.11.07.467589.full AB - Animals integrate external stimuli to shape their physiological responses throughout development. In adverse environments, Caenorhabditis elegans larvae can enter a stress-resistant diapause state with arrested metabolism and reproductive physiology. Amphid sensory neurons feed into both rapid chemotactic and shortterm foraging mode decisions, mediated by amphid and pre-motor interneurons, as well as the long-term diapause decision. We identify amphid interneurons that integrate pheromone cues and propagate this information via a neuropeptidergic pathways to influence larval developmental fate, bypassing the pre-motor system. AIA interneuron-derived FLP-2 neuropeptide signaling promotes reproductive growth and AIA activity is suppressed by pheromone. FLP-2 acts antagonistically to the insulin-like INS-1. FLP-2’s growth promoting effects are inhibited by upstream metabotropic glutamatergic signaling and mediated by the broadly-expressed neuropeptide receptor NPR-30. Conversely, the AIB interneurons and their neuropeptide receptor NPR-9/GALR2 promote diapause entry. These neuropeptidergic outputs allow reuse of parts of a sensory system for a decision with a distinct timescale.Competing Interest StatementThe authors have declared no competing interest.