Interneuron control of C. elegans developmental decision-making.

Natural environments are highly dynamic, and this complexity challenges animals to accurately integrate external cues to shape their responses. Adaptive developmental plasticity enables organisms to remodel their physiology, morphology, and behavior to better suit the predicted future environment and ultimately enhance their ecological success.1 Understanding how an animal generates a neural representation of current and forecasted environmental conditions and converts these circuit computations into a predictive adaptive physiological response may provide fundamental insights into the molecular and cellular basis of decision-making over developmentally relevant timescales. Although it is known that sensory cues usually trigger the developmental switch and that downstream inter-tissue signaling pathways enact the alternative developmental phenotype, the integrative neural mechanisms that transduce external inputs into effector pathways are less clear.2,3 In adverse environments, Caenorhabditis elegans larvae can enter a stress-resistant diapause state with arrested metabolism and reproductive physiology.4 Amphid sensory neurons feed into both rapid chemotactic and short-term foraging mode decisions, mediated by amphid and pre-motor interneurons, as well as the long-term diapause entry decision. Here, we identify amphid interneurons that integrate pheromone cues and propagate this information via a neuropeptidergic pathway 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 pheromones. FLP-2 signaling is inhibited by upstream glutamatergic transmission via the metabotropic receptor MGL-1 and mediated by the broadly expressed neuropeptide G-protein-coupled receptor NPR-30. Thus, metabotropic signaling allows the reuse of parts of a sensory system for a decision with a distinct timescale.