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Small-molecule pheromones that control dauer development in Caenorhabditis elegans

Abstract

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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Acknowledgements

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

Authors

Contributions

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.

Corresponding author

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). https://doi.org/10.1038/nchembio.2007.3

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  • DOI: https://doi.org/10.1038/nchembio.2007.3

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