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Small-molecule pheromones that control dauer development in Caenorhabditis elegans


In response to high population density or low food supply, the nematode Caenorhabditis elegans enters an alternative larval stage, known as the dauer, that can withstand adverse conditions for prolonged periods. C. elegans senses its population density through a small-molecule signal, traditionally called the dauer pheromone, that it secretes into its surroundings. Here we show that the dauer pheromone consists of several structurally related ascarosides—derivatives of the dideoxysugar ascarylose—and that two of these ascarosides (1 and 2) are roughly two orders of magnitude more potent at inducing dauer formation than a previously reported dauer pheromone component (3) and constitute a physiologically relevant signal. The identification of dauer pheromone components 1 and 2 will facilitate the identification of target receptors and downstream signaling proteins.

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Figure 1: Structures of ascarosides 1, 2 and 3.
Figure 2: Comparison of the activities of 1, 2 and 3 in the dauer formation assay.

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  1. Eberhard, A. et al. Structural identification of autoinducer of Photobacterium fischeri luciferase. Biochemistry 20, 2444–2449 (1981).

    Article  CAS  Google Scholar 

  2. Taga, M.E. & Bassler, B.L. Chemical communication among bacteria. Proc. Natl. Acad. Sci. USA 100, 14549–14554 (2003).

    Article  CAS  Google Scholar 

  3. Golden, J.W. & Riddle, D.L. The Caenorhabditis elegans dauer larva: developmental effects of pheromone, food, and temperature. Dev. Biol. 102, 368–378 (1984).

    Article  CAS  Google Scholar 

  4. Cassada, R.C. & Russell, R.L. The dauerlarva, a post-embryonic developmental variant of the nematode Caenorhabditis elegans. Dev. Biol. 46, 326–342 (1975).

    Article  CAS  Google Scholar 

  5. Klass, M. & Hirsh, D. Non-ageing developmental variant of Caenorhabditis elegans. Nature 260, 523–525 (1976).

    Article  CAS  Google Scholar 

  6. Golden, J.W. & Riddle, D.L. A pheromone-induced developmental switch in Caenorhabditis elegans: temperature-sensitive mutants reveal a wild-type temperature-dependent process. Proc. Natl. Acad. Sci. USA 81, 819–823 (1984).

    Article  CAS  Google Scholar 

  7. Vowels, J.J. & Thomas, J.H. Genetic analysis of chemosensory control of dauer formation in Caenorhabditis elegans. Genetics 130, 105–123 (1992).

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Thomas, J.H., Birnby, D.A. & Vowels, J.J. Evidence for parallel processing of sensory information controlling dauer formation in Caenorhabditis elegans. Genetics 134, 1105–1117 (1993).

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Ren, P. et al. Control of C. elegans larval development by neuronal expression of a TGFβ homolog. Science 274, 1389–1391 (1996).

    Article  CAS  Google Scholar 

  10. Patterson, G.I. & Padgett, R.W. TGFβ-related pathways. Roles in Caenorhabditis elegans development. Trends Genet. 16, 27–33 (2000).

    Article  CAS  Google Scholar 

  11. Kimura, K.D., Tissenbaum, H.A., Liu, Y. & Ruvkun, G. daf-2, an insulin receptor-like gene that regulates longevity and diapause in Caenorhabditis elegans. Science 277, 942–946 (1997).

    Article  CAS  Google Scholar 

  12. Braeckman, B.P., Houthoofd, K. & Vanfleteren, J.R. Insulin-like signaling, metabolism, stress resistance and aging in Caenorhabditis elegans. Mech. Ageing Dev. 122, 673–693 (2001).

    Article  CAS  Google Scholar 

  13. Finch, C.E. & Ruvkun, G. The genetics of aging. Annu. Rev. Genomics Hum. Genet. 2, 435–462 (2001).

    Article  CAS  Google Scholar 

  14. Golden, J.W. & Riddle, D.L. A pheromone influences larval development in the nematode Caenorhabditis elegans. Science 218, 578–580 (1982).

    Article  CAS  Google Scholar 

  15. Golden, J.W. & Riddle, D.L. A Caenorhabditis elegans dauer-inducing pheromone and and antagonistic component of the food supply. J. Chem. Ecol. 10, 1265–1280 (1984).

    Article  CAS  Google Scholar 

  16. Jeong, P.Y. et al. Chemical structure and biological activity of the Caenorhabditis elegans dauer-inducing pheromone. Nature 433, 541–545 (2005).

    Article  CAS  Google Scholar 

  17. Law, J.H. & Regnier, F.E. Pheromones. Annu. Rev. Biochem. 40, 533–548 (1971).

    Article  CAS  Google Scholar 

  18. Keeling, C.I., Slessor, K.N., Higo, H.A. & Winston, M.L. New components of the honey bee (Apis mellifera L.) queen retinue pheromone. Proc. Natl. Acad. Sci. USA 100, 4486–4491 (2003).

    Article  CAS  Google Scholar 

  19. Golden, J.W. & Riddle, D.L. A gene affecting production of the Caenorhabditis elegans dauer-inducing pheromone. Mol. Gen. Genet. 198, 534–536 (1985).

    Article  CAS  Google Scholar 

  20. Perkins, L.A., Hedgecock, E.M., Thomson, J.N. & Culotti, J.G. Mutant sensory cilia in the nematode Caenorhabditis elegans. Dev. Biol. 117, 456–487 (1986).

    Article  CAS  Google Scholar 

  21. Bargmann, C.I. & Horvitz, H.R. Control of larval development by chemosensory neurons in Caenorhabditis elegans. Science 251, 1243–1246 (1991).

    Article  CAS  Google Scholar 

  22. Coburn, C.M. & Bargmann, C.I. A putative cyclic nucleotide-gated channel is required for sensory development and function in C. elegans. Neuron 17, 695–706 (1996).

    Article  CAS  Google Scholar 

  23. Zwaal, R.R., Mendel, J.E., Sternberg, P.W. & Plasterk, R.H. Two neuronal G proteins are involved in chemosensation of the Caenorhabditis elegans dauer-inducing pheromone. Genetics 145, 715–727 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Birnby, D.A. et al. A transmembrane guanylyl cyclase (DAF-11) and Hsp90 (DAF-21) regulate a common set of chemosensory behaviors in Caenorhabditis elegans. Genetics 155, 85–104 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Sulston, J. & Hodgkin, J. in The Nematode Caenorhabditis elegans (ed. Wood, W.B.) 587–606 (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York, USA, 1988).

    Google Scholar 

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We thank H.Y. Mak and G. Ruvkun (Harvard Medical School) for advice regarding the culturing of worms and for supplying worm strains and a microscope. We also thank C. Bargmann (Rockefeller University) for advice and strains. This work was supported by CA24487 (J.C.). R.A.B. is the recipient of a National Research Service Award postdoctoral fellowship from the US National Institutes of Health. M.F. was supported by a Japan Society for the Promotion of Science Fellowship.

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Authors and Affiliations



R.A.B. designed experiments, performed biological experiments and wrote the manuscript; M.F. performed structure elucidation and biological experiments; F.C.S. performed structure elucidation and chemical synthesis; J.C. designed experiments and wrote the manuscript.

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Correspondence to Jon Clardy.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Fig. 1

NMR spectra of natural 1 in methanol-d4. (PDF 879 kb)

Supplementary Fig. 2

Key COSY interactions and HMBC interactions. (PDF 8 kb)

Supplementary Fig. 3

Establishing the stereochemistry of 1. (PDF 78 kb)

Supplementary Fig. 4

NMR spectra of synthetic 2 in methanol-d4. (PDF 172 kb)

Supplementary Fig. 5

Comparison of the activities of 1, 2, and 3 in the dauer formation assay in different mutant backgrounds at 20 °C. (PDF 47 kb)

Supplementary Fig. 6

Percent dauer formation in wild-type and daf-22 worms. (PDF 44 kb)

Supplementary Table 1

1H, 13C NMR and HMBC data for 1 in methanol-d4. (PDF 18 kb)

Supplementary Table 2

1H and 13C NMR data for 2 in acetone-d6 derived from dqf-COSY, HMQC, and HMBC spectra. (PDF 19 kb)

Supplementary Methods (PDF 94 kb)

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Butcher, R., Fujita, M., Schroeder, F. et al. Small-molecule pheromones that control dauer development in Caenorhabditis elegans. Nat Chem Biol 3, 420–422 (2007).

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