UMass Chan Medical School Faculty Publications

UMMS Affiliation

Neurobiology Department; Alkema Lab

Publication Date


Document Type



Amino Acids, Peptides, and Proteins | Behavioral Neurobiology | Molecular and Cellular Neuroscience


Dioecious species are a hallmark of the animal kingdom, with opposing sexes responding differently to identical sensory cues. Here, we study the response of C. elegans to the small-molecule pheromone, ascr#8, which elicits opposing behavioral valences in each sex. We identify a novel neuropeptide-neuropeptide receptor (NP/NPR) module that is active in males, but not in hermaphrodites. Using a novel paradigm of neuropeptide rescue that we established, we leverage bacterial expression of individual peptides to rescue the sex-specific response to ascr#8. Concurrent biochemical studies confirmed individual FLP-3 peptides differentially activate two divergent receptors, NPR-10 and FRPR-16. Interestingly, the two of the peptides that rescued behavior in our feeding paradigm are related through a conserved threonine, suggesting that a specific NP/NPR combination sets a male state, driving the correct behavioral valence of the ascr#8 response. Receptor expression within pre-motor neurons reveals novel coordination of male-specific and core locomotory circuitries.


Cellular neuroscience, Neural circuits

Rights and Permissions

Copyright © The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit

DOI of Published Version



Reilly DK, McGlame EJ, Vandewyer E, Robidoux AN, Muirhead CS, Northcott HT, Joyce W, Alkema MJ, Gegear RJ, Beets I, Srinivasan J. Distinct neuropeptide-receptor modules regulate a sex-specific behavioral response to a pheromone. Commun Biol. 2021 Aug 31;4(1):1018. doi: 10.1038/s42003-021-02547-7. PMID: 34465863; PMCID: PMC8408276. Link to article on publisher's site

Related Resources

Link to Article in PubMed

Journal/Book/Conference Title

Communications biology

PubMed ID


Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.