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FMRFamide neuropeptides and acetylcholine synergistically inhibit egg-laying by C. elegans

Nature Neuroscience volume 11, pages 1168–1176 (2008)Cite this article

Abstract

Egg-laying behavior of the Caenorhabditis elegans hermaphrodite is regulated by G protein signaling pathways. Here we show that the egg laying–defective mutant egl-6(n592) carries an activating mutation in a G protein–coupled receptor that inhibits C. elegans egg-laying motor neurons in a Go-dependent manner. Ligands for EGL-6 are Phe-Met-Arg-Phe-NH2 (FMRFamide)-related peptides encoded by the genes flp-10 and flp-17. flp-10 is expressed in both neurons and non-neuronal cells. The major source of flp-17 peptides is a pair of presumptive sensory neurons, the BAG neurons. Genetic analysis of the egl-6 pathway revealed that the EGL-6 neuropeptide signaling pathway functions redundantly with acetylcholine to inhibit egg-laying. The retention of embryos in the uterus of the C. elegans hermaphrodite is therefore under the control of a presumptive sensory system and is inhibited by the convergence of signals from neuropeptides and the small-molecule neurotransmitter acetylcholine.

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Figure 1: egl-6 encodes two isoforms of a seven-pass transmembrane receptor.
Figure 2: egl-6(gf) inhibition of egg-laying requires Go signaling.
Figure 3: egl-6 expression in the HSN motor neurons inhibits egg-laying.
Figure 4: flp-10 and flp-17 encode ligands for the EGL-6 receptor.
Figure 5: The EGL-6 receptor is regulated by flp-10 and flp-17 in vivo.
Figure 6: flp-10 and flp-17 are expressed in different cells.
Figure 7: The BAG sensory neurons inhibit egg-laying.
Figure 8: EGL-6 signaling inhibits egg-laying behavior redundantly with acetylcholine.

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Acknowledgements

We thank Y. Kohara for flp-10 and flp-17 cDNAs; N. Dascal for GIRK1 and GIRK4 expression constructs; J. Rand for unc-17 cha-1 strains; J. Moresco and M. Koelle for tph-1 promoter constructs; A. Fire for expression vectors; A. Hellman, S. McGonagle, B. Castor and N. An for technical assistance; N. Abe and R. O'Hagan for help with Xenopus oocyte electrophysiology; J. Chung for help with data analysis; and B. Galvin and A. Saffer for critical reading of the manuscript. N.R. received support from the Howard Hughes Medical Institute, the Life Sciences Research Foundation and the Medical Foundation. H.R.H. is a David H. Koch Professor of Biology and an Investigator of the Howard Hughes Medical Institute. This work was supported by National Institutes of Health grant GM24663.

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  1. Department of Biology, Howard Hughes Medical Institute, McGovern Institute for Brain Research, 68-425, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, 02139, Massachusetts, USA

    Niels Ringstad & H Robert Horvitz

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N.R. performed all experiments. N.R. and H.R.H. designed the experiments and wrote the manuscript.

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Correspondence to H Robert Horvitz.

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Ringstad, N., Horvitz, H. FMRFamide neuropeptides and acetylcholine synergistically inhibit egg-laying by C. elegans. Nat Neurosci 11, 1168–1176 (2008). https://doi.org/10.1038/nn.2186

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