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

Abstract

<p id="d10031863e253">Under environmental stress, animals can adopt different forms and behaviors through phenotypic plasticity. The roundworm <i>Caenorhabditis elegans</i> can exit reproductive growth and enter the stress-resistant dauer larval stage. We investigated phenotypic plasticity in a whole organism by comparing gene expression during dauer and reproductive development using RNA sequencing. As animals entered dauer, we observed striking up-regulation of neuronal signaling peptides, which promote the dauer-entry decision instead of reproductive growth. These neuropeptides also enable new behaviors in dauers for exploiting carrier animals for dispersal. Neuropeptides are similarly up-regulated in the infective, dauer-like stages of parasitic roundworms, indicating dauer as a strong model for studying parasitic behaviors. Our investigation reveals that neuropeptides can alter developmental decision-making and behavior in stressed <i>C. elegans</i>. </p><p class="first" id="d10031863e262">Animals, including humans, can adapt to environmental stress through phenotypic plasticity. The free-living nematode <i>Caenorhabditis elegans</i> 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 <i>sbt-1</i> 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 <i>flp-10</i> and <i>flp-17</i> mimic the effects of <i>sbt-1</i> on 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 <i>C. elegans</i> enhances their decision-making accuracy and expands their behavioral repertoire. </p>