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A blend of small molecules regulates both mating and development in Caenorhabditis elegans

Srinivasan, Jagan and Kaplan, Fatma and Ajredini, Ramadan and Zachariah, Cherian and Alborn, Hans T. and Teal, Peter E. A. and Malik, Rabia U. and Edison, Arthur S. and Sternberg, Paul W. and Schroeder, Frank C. (2008) A blend of small molecules regulates both mating and development in Caenorhabditis elegans. Nature, 454 (7208). pp. 1115-1118. ISSN 0028-0836. PMCID PMC2774729.

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In many organisms, population-density sensing and sexual attraction rely on small-molecule-based signalling systems. In the nematode Caenorhabditis elegans, population density is monitored through specific glycosides of the dideoxysugar ascarylose (the ‘ascarosides’) that promote entry into an alternative 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, by means of combinatorial activity-guided fractionation of the C. elegans metabolome, that the mating signal consists of a synergistic blend of three dauer-inducing ascarosides, which we call ascr#2, ascr#3 and ascr#4. This blend of ascarosides acts as a potent male attractant at very low concentrations, whereas at the higher concentrations required for dauer formation the compounds no longer attract males and instead deter hermaphrodites. The ascarosides ascr#2 and ascr#3 carry different, but overlapping, information, as ascr#3 is more potent as a male attractant than ascr#2, whereas ascr#2 is slightly more potent than ascr#3 in promoting dauer formation7. We demonstrate that ascr#2, ascr#3 and ascr#4 are strongly synergistic, and that two types of neuron, the amphid single-ciliated sensory neuron type K (ASK) and the male-specific cephalic companion neuron (CEM), are required for male attraction by ascr#3. On the basis of these results, male attraction and dauer formation in C. elegans appear as alternative behavioural responses to a common set of signalling molecules. The ascaroside signalling system thus connects reproductive and developmental pathways and represents a unique example of structure- and concentration-dependent differential activity of signalling molecules.

Item Type:Article
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URLURL TypeDescription ReadCube access CentralArticle
Srinivasan, Jagan0000-0001-5449-7938
Kaplan, Fatma0000-0002-9565-0211
Alborn, Hans T.0000-0003-3918-5041
Edison, Arthur S.0000-0002-5686-2350
Sternberg, Paul W.0000-0002-7699-0173
Schroeder, Frank C.0000-0002-4420-0237
Additional Information:© 2008 Macmillan Publishers Limited. Received 17 January 2008; Accepted 13 June 2008; Published 23 July 2008. This work was supported by the Human Frontiers Science Program (A.S.E., P.W.S. and P.E.A.T.), a US National Institutes of Health grant (P41 GM079571) to F.C.S., and the Howard Hughes Medical Institute, of which J.S. is an associate and P.W.S. an investigator. NMR data were collected in the UF-AMRIS facility; we thank J. Rocca for assistance. We thank E. Peden and D. Xue for the ceh-30 strains, C. J. Cronin and A. Choe for advice on behavioural assays, L. R. Baugh for liquid-culture dauer formation assays, B. Fox for assistance with the synthesis of ascr#2, ascr#3 and ascr#4, and M. de Bono, A. Dossey and M. Stadler for discussions. E. Hallem, J. Bungert and D. Hutchinson provided comments on the manuscript. Author Contributions J.S. and P.W.S. designed the biological experiments and J.S. performed all the biological experiments; F.K. developed the procedure for collecting secreted worm metabolites and designed the chemical experiments and fractionation; F.K. and R.A. produced worm-conditioned water and performed chromatography; F.K., F.C.S., R.U.M., C.Z. and A.S.E. performed structure elucidation by NMR; H.T.A. performed structure elucidation by LC-MS; F.C.S. synthesized ascr#2, ascr#3 and ascr#4; and J.S., F.K., F.C.S., A.S.E., P.E.A.T. and P.W.S. analysed the data and wrote the paper. Jagan Srinivasan & Fatma Kaplan: These authors contributed equally to this work.
Funding AgencyGrant Number
Human Frontier Science ProgramUNSPECIFIED
NIHP41 GM079571
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
Issue or Number:7208
PubMed Central ID:PMC2774729
Record Number:CaltechAUTHORS:20190514-083519984
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:95469
Deposited By: Tony Diaz
Deposited On:14 May 2019 21:15
Last Modified:03 Oct 2019 21:13

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