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Published December 12, 2017 | Supplemental Material + Published
Journal Article Open

FMRFamide-like peptides expand the behavioral repertoire of a densely connected nervous system


Animals, including humans, can adapt to environmental stress through phenotypic plasticity. The free-living nematode Caenorhabditis elegans can adapt to harsh environments by undergoing a whole-animal change, involving exiting reproductive development and entering the stress-resistant dauer larval stage. The dauer is a dispersal stage with dauer-specific behaviors for finding and stowing onto carrier animals, but how dauers acquire these behaviors, despite having a physically limited nervous system of 302 neurons, is poorly understood. We compared dauer and reproductive development using whole-animal RNA sequencing at fine time points and at sufficient depth to measure transcriptional changes within single cells. We detected 8,042 genes differentially expressed during dauer and reproductive development and observed striking up-regulation of neuropeptide genes during dauer entry. We knocked down neuropeptide processing using sbt-1 mutants and demonstrate that neuropeptide signaling promotes the decision to enter dauer rather than reproductive development. We also demonstrate that during dauer neuropeptides modulate the dauer-specific nictation behavior (carrier animal-hitchhiking) and are necessary for switching from repulsion to CO_2 (a carrier animal cue) in nondauers to CO_2 attraction in dauers. We tested individual neuropeptides using CRISPR knockouts and existing strains and demonstrate that the combined effects of flp-10 and flp-17 mimic the effects of sbt-1on nictation and CO_2 attraction. Through meta-analysis, we discovered similar up-regulation of neuropeptides in the dauer-like infective juveniles of diverse parasitic nematodes, suggesting the antiparasitic target potential of SBT-1. Our findings reveal that, under stress, increased neuropeptide signaling in C. elegans enhances their decision-making accuracy and expands their behavioral repertoire.

Additional Information

© 2017 National Academy of Sciences. Published under the PNAS license. Contributed by Paul W. Sternberg, October 31, 2017 (sent for review June 8, 2017; reviewed by Junho Lee and Chris Li). Published online before print November 22, 2017. We thank Daehan Lee for providing the nictation microchip design; Elissa Hallem for advice on CO_2 assays; Christopher Cronin for advice on behavioral assay setups; Mihoko Kato, Hillel Schwartz, Igor Antoshechkin, Ryoji Shinya, Han Wang, Animesh Ray, and Jonathan Liu for critically reading the manuscript; the Caenorhabditis Genetics Center, which is funded by the NIH Office of Research Infrastructure Programs (Grant P40 OD010440), and Adam Antebi, Mario de Bono, and H. Robert Horvitz for providing animal strains; WormBase and WormBase SPELL for tools, datasets, and invaluable information; and the Millard and Muriel Jacobs Genetics and Genomics Laboratory for support with library construction and sequencing. Author contributions: J.S.L., P.-Y.S., O.N.S., and P.W.S. designed research; J.S.L., P.-Y.S., and O.N.S. performed research; J.S.L., P.-Y.S., O.N.S., and P.Q.-C. contributed new reagents/analytic tools; J.S.L., P.-Y.S., O.N.S., P.Q.-C., and A.K.R. analyzed data; and J.S.L., P.-Y.S., O.N.S., P.Q.-C., and P.W.S. wrote the paper. Reviewers: J.L., Seoul National University; and C.L., City College of New York. The authors declare no conflict of interest. Data deposition: The RNA-seq data in this paper have been deposited in the National Center for Biotechnology Information Sequence Read Archive (SRA) database (accession no. SRP116980). Codes used for data analysis have been deposited in GitHub and are available at https://github.com/WormLabCaltech/dauerRNAseq. This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1710374114/-/DCSupplemental.

Attached Files

Published - PNAS-2017-Lee-E10726-35.pdf

Supplemental Material - pnas.1710374114.sd01.xlsx

Supplemental Material - pnas.1710374114.sd02.xlsx

Supplemental Material - pnas.1710374114.sd03.xlsx

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Supplemental Material - pnas.1710374114.sd05.xlsx

Supplemental Material - pnas.1710374114.sm01.wmv

Supplemental Material - pnas.1710374114.sm02.wmv

Supplemental Material - pnas.1710374114.sm03.avi

Supplemental Material - pnas.1710374114.sm04.avi

Supplemental Material - pnas.1710374114.sm05.avi

Supplemental Material - pnas.1710374114.sm06.avi

Supplemental Material - pnas.201710374SI.pdf


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August 21, 2023
October 17, 2023