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Interneuron control of C. elegans developmental decision-making

Chai, Cynthia M. and Torkashvand, Mahdi and Seyedolmohadesin, Maedeh and Park, Heenam and Venkatachalam, Vivek and Sternberg, Paul W. (2022) Interneuron control of C. elegans developmental decision-making. Current Biology, 32 (10). pp. 2316-2324. ISSN 0960-9822. PMCID PMC9270850. doi:10.1016/j.cub.2022.03.077.

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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. 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. 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 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.

Item Type:Article
Related URLs:
URLURL TypeDescription Paper ItemCode
Chai, Cynthia M.0000-0001-6118-2926
Torkashvand, Mahdi0000-0002-4381-0367
Seyedolmohadesin, Maedeh0000-0003-3742-394X
Park, Heenam0000-0001-7911-5828
Venkatachalam, Vivek0000-0002-2414-7416
Sternberg, Paul W.0000-0002-7699-0173
Additional Information:© 2022 Elsevier Inc. Received 10 November 2021, Revised 13 March 2022, Accepted 30 March 2022, Available online 20 April 2022. Some strains were provided by the CGC, which is funded by NIH Office of Research Infrastructure Programs (P40 OD010440). Some strains were provided by the lab of Dr. Shohei Mitani as part of the National Bioresource Project. Figure 1A was generated with P.W.S., C.M.C., and H.P. were supported by NIH grants R24OD023041, UF1NS111697, and R21MH115454. V.V., M.T., and M.S. were supported by a Burroughs Wellcome Fund Career Award at the Scientific Interface and the American Federation for Aging Research. Author contributions: Conceptualization, C.M.C. and P.W.S.; methodology, C.M.C., V.V., and M.T.; crude pheromone extraction, dauer formation assays, coelomocyte uptake assays, molecular cloning, transgenesis, and microscopy, C.M.C.; calcium imaging experiments, M.T. and M.S.; CRISPR mutagenesis, H.P.; data analysis and visualization, C.M.C., M.T., and M.S.; funding acquisition, P.W.S. and V.V.; writing the paper with input from coauthors, C.M.C. The authors declare no competing interests. Data and code availability: All data reported in this paper will be shared by the lead contact upon request. All original code used for calcium imaging experiments has been deposited at and is publicly available as of the date of publication. Any additional information required to reanalyze the data reported in this paper is available from the lead contact upon request.
Funding AgencyGrant Number
NIHP40 OD010440
Burroughs Wellcome FundUNSPECIFIED
American Federation for Aging ResearchUNSPECIFIED
Subject Keywords:developmental plasticity; interneuron; neuropeptide; G-protein coupled receptor; pheromone; circuits; metabotropic glutamate receptor; physiology; metabolism
Issue or Number:10
PubMed Central ID:PMC9270850
Record Number:CaltechAUTHORS:20211115-191646400
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Official Citation:Cynthia M. Chai, Mahdi Torkashvand, Maedeh Seyedolmohadesin, Heenam Park, Vivek Venkatachalam, Paul W. Sternberg, Interneuron control of C. elegans developmental decision-making, Current Biology, Volume 32, Issue 10, 2022, Pages 2316-2324.e4, ISSN 0960-9822,
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:111872
Deposited By: Tony Diaz
Deposited On:15 Nov 2021 19:27
Last Modified:20 Jul 2022 17:15

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