The free-living nematode C. elegans has been used extensively as a model system for social behaviors such as foraging, population density sensing, mating, and aggregation. Recently a family of small molecule signals, the ascarosides have been shown to control both population density sensing and mating behavior 1. We hypothesized that C. elegans aggregation behavior is also mediated by small-molecule signals as no intraspecific signals promoting attraction or aggregation of wild-type hermaphrodites have been identified. Using a comparative metabolomics approach 2, we have isolated a novel group of ascarosides that incorporates an indole moiety in the ascaroside structure. Behavioral assays demonstrated 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 to hermaphrodites3. Hermaphrodite attraction to indole ascarosides is dependent on the ASK-amphid sensory neurons. Previous studies have shown that the ring interneuron RMG integrates attraction and aggregation signals from ASK and other sensory neurons3. However, we found that attraction to indole ascarosides does not require the RMG interneurons. 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, independently of
npr-1 locus. The identification of indole ascarosides as aggregation signals reveals a highly developed chemical language for social communication in C. elegans. 1. Srinivasan, J. et al. (2008). A blend of small molecules regulates both mating and development in Caenorhabditis elegans. Nature 454, 1115. 2. Pungaliya, C., et al. (2009). A shortcut to identifying small molecule signals that regulate behavior and development in Caenorhabditis elegans. Proc Natl Acad Sci U S A 106, 7708. 3. Macosko, E.Z et al (2009). A hub-and-spoke circuit drives pheromone attraction and social behavior in C. elegans. Nature 458, 1171.