A Modular Library of Small Molecule Signals Regulates Social Behaviors in Caenorhabditis elegans
Abstract
The nematode C. elegans is an important model for the study of social behaviors. Recent investigations have shown that a family of small molecule signals, the ascarosides, controls population density sensing and mating behavior. However, despite extensive studies of C. elegans aggregation behaviors, no intraspecific signals promoting attraction or aggregation of wild-type hermaphrodites have been identified. Using comparative metabolomics, we show that the known ascarosides are accompanied by a series of derivatives featuring a tryptophan-derived indole moiety. Behavioral assays demonstrate that these indole ascarosides serve as potent intraspecific attraction and aggregation signals for hermaphrodites, in contrast to ascarosides lacking the indole group, which are repulsive. Hermaphrodite attraction to indole ascarosides depends on the ASK amphid sensory neurons. Downstream of the ASK sensory neuron, the interneuron AIA is required for mediating attraction to indole ascarosides instead of the RMG interneurons, which previous studies have shown to integrate attraction and aggregation signals from ASK and other sensory neurons. The role of the RMG interneuron in mediating aggregation and attraction is thought to depend on the neuropeptide Y-like receptor NPR-1, because solitary and social C. elegans strains are distinguished by different npr-1 variants. We show that indole ascarosides promote attraction and aggregation in both solitary and social C. elegans strains. The identification of indole ascarosides as aggregation signals reveals unexpected complexity of social signaling in C. elegans, which appears to be based on a modular library of ascarosides integrating building blocks derived from lipid β-oxidation and amino-acid metabolism. Variation of modules results in strongly altered signaling content, as addition of a tryptophan-derived indole unit to repellent ascarosides produces strongly attractive indole ascarosides. Our findings show that the library of ascarosides represents a highly developed chemical language integrating different neurophysiological pathways to mediate social communication in C. elegans.
Additional Information
© 2012 Srinivasan et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Received August 22, 2011; Accepted November 22, 2011; Published January 10, 2012. This work was supported in part by a National Institutes of Health grant (GM088290 to FCS and GM085285 to ASE, FCS, and PWS), and the Howard Hughes Medical Institute, with which PWS is an Investigator. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We thank Hillel Schwartz, David Prober, and Fatma Kaplan for helpful discussions; Christopher J. Cronin and Yang Hu for help with tracker experiments; and Cornelia Bargmann, Takeshi Ishihara, and Tokumitsu Wakabayashi for sharing worm strains. Author Contributions: The author(s) have made the following declarations about their contributions: Conceived and designed the experiments: JS SHV ASE PWS FCS. Performed the experiments: JS SHV NB AZ PM FCS. Analyzed the data: JS SHVR NB AZ PM FCS. Contributed reagents/ materials/analysis tools: OGO MCH. Wrote the paper: JS SHV PWS FCS.Attached Files
Published - Srinivasan2012p17375Plos_Biol.pdf
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Additional details
- PMCID
- PMC3254649
- Eprint ID
- 29738
- Resolver ID
- CaltechAUTHORS:20120315-161720438
- NIH
- GM088290
- NIH
- GM085285
- Howard Hughes Medical Institute (HHMI)
- Created
-
2012-03-16Created from EPrint's datestamp field
- Updated
-
2021-11-09Created from EPrint's last_modified field