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A class of secreted small-molecule pheromones, termed ascarosides, play an important role in olfactory perception by affecting biological functions ranging from development to behavior. The ascaroside #8 (ascr#8) mediates sex-specific behaviors, driving avoidance in hermaphrodites and attraction in males. Males sense ascr#8 via the ciliated male-specific cephalic sensory (CEM) neurons, which exhibit radial symmetry along dorsal\u2013ventral and left\u2013right axes. Calcium imaging studies suggest a complex neural coding mechanism that translates stochastic physiological responses in these neurons to reliable behavioral outputs. To test the hypothesis that neurophysiological complexity arises from differential expression of genes, we performed cell-specific transcriptomic profiling; this revealed between 18 and 62 genes with at least twofold higher expression in a specific CEM neuron subtype vs both other CEM neurons and adult males. These included two G protein\u2013coupled receptor (GPCR) genes, srw-97 and dmsr-12, that were specifically expressed in nonoverlapping subsets of CEM neurons and whose expression was confirmed by GFP reporter analysis. Single CRISPR-Cas9 knockouts of either srw-97 or dmsr-12 resulted in partial defects, while a double knockout of both srw-97 and dmsr-12 completely abolished the attractive response to ascr#8. Together, our results suggest that the evolutionarily distinct GPCRs SRW-97 and DMSR-12 act nonredundantly in discrete olfactory neurons to facilitate male-specific sensation of ascr#8.<\/jats:p>","DOI":"10.1093\/genetics\/iyad026","type":"journal-article","created":{"date-parts":[[2023,2,18]],"date-time":"2023-02-18T19:52:42Z","timestamp":1676749962000},"source":"Crossref","is-referenced-by-count":9,"title":["Transcriptomic profiling of sex-specific olfactory neurons reveals subset-specific receptor expression in <i>Caenorhabditis elegans<\/i>"],"prefix":"10.1093","volume":"223","author":[{"given":"Douglas K","family":"Reilly","sequence":"first","affiliation":[{"name":"Department of Biology and Biotechnology, Worcester Polytechnic Institute , Worcester, MA 01605 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erich M","family":"Schwarz","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genetics, Cornell University , Ithaca, NY 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