Submitted to: Nature
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/30/2008
Publication Date: 8/1/2008
Citation: Srinivasan, J., Kaplan, F., Ajredini, R., Zachariah, C., Alborn, H.T., Teal, P.E., Edison, A.S., Sternberg, P.W., Schroeder, F.C. 2008. A blend of small molecules regulates both mating and development in Caenorhabditis elegans. Nature Magazine. 454(28):1115-1119. Interpretive Summary: The nematode Caenorhabditis elegans has been utilized extensively since the early 1970’s as a model organism for studies of molecular and developmental biology.C. elegans, that is one of the simplest organisms with a nervous system, is an important organism for exploring the neural mechanisms responsible for behaviors such as chemotaxis, thermotaxis and mating behavior. In many organisms, population density sensing and sexual attraction rely on small molecule-based signaling systems. Until now only the chemical signals that promote larval C. elegans entry into the non-feeding and highly persistent dauer stage have been identified. Scientists at USDA ARS CMAVE in Gainesville Florida in co-operation with scientists at University of Florida, California Institute of technology and Cornell University discovered that both mating behavior and dauer formation are regulated by largely overlapping families of small chemically related molecules, named ascarosided. Characterization of the receptors of the ascarosides and their downstream targets will provide further insights in how developmental and reproductive pathways are connected.
Technical Abstract: In many organisms, population density sensing and sexual attraction rely on small molecule-based signaling systems. In the nematode Caenorhabditis elegans, population density is monitored via specific glycosides of the dideoxysugar ascarylose that promote entry into an alternate larval stage, the non-feeding and highly persistent dauer stage. In addition, adult C. elegans males are attracted to hermaphrodites by a previously unidentified small-molecule signal. Here we show via combinatorial activity-guided fractionation of worm-conditioned water that the mating signal in C. elegans consists of a synergistic blend of small molecules that includes two of the dauer-inducing ascarosides. The dauer-inducing ascarosides are active as male attractants only at concentrations significantly lower than required for dauer induction, whereas at the higher concentrations required for dauer formation, the compounds no longer attract males and deter hermaphrodites. We demonstrate that the ascarosides ascr#2 and ascr#3 carry different though overlapping information, as ascr#3 is more potent as a male attractant than ascr#2,whereas in the dauer assay ascr#2 is slightly more potent than ascr#37. Male attraction is further enhanced by a third component, a novel glycosylated ascaroside (ascr#4). Male attraction by ascr#2, ascr#3, and ascr#4 is strongly synergistic, suggesting different molecular targets converge on a common pathway(s). Based on our results, mating attraction and dauer formation appear as alternative behavioral responses to a common set of signaling molecules. The C. elegans ascaroside signaling system thus connects reproductive and developmental pathways and represents a unique example of structure and concentration-dependent differential activity of signaling molecules.