RT Journal Article SR Electronic T1 Transcriptomic profiling of sex-specific olfactory neurons reveals subset-specific receptor expression in C. elegans JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.10.26.465928 DO 10.1101/2021.10.26.465928 A1 Douglas K. Reilly A1 Erich M. Schwarz A1 Caroline S. Muirhead A1 Annalise N. Robidoux A1 Igor Antoshechkin A1 Anusha Narayan A1 Meenakshi K. Doma A1 Paul W. Sternberg A1 Jagan Srinivasan YR 2021 UL http://biorxiv.org/content/early/2021/10/28/2021.10.26.465928.abstract AB The nematode Caenorhabditis elegans utilizes chemosensation to navigate an ever-changing environment for its survival. A class of secreted small-molecule pheromones, termed ascarosides, play an important role in olfactory perception by affecting a host of biological function ranging from development to behavior. The ascaroside 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-ventral and left-right 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 the neurophysiological complexity arises from differential expression of genes within subsets of these neurons, we performed cell-specific transcriptomic profiling of these sensory neurons. Expression profiling revealed between 20 and 639 genes enriched at least two-fold per CEM neuron and identified multiple G protein coupled receptor (GPCR) candidates enriched in non-overlapping subsets of CEM neurons. GFP reporter analysis confirmed that RNA expression of two of the GPCR genes, srw-97 and dmsr-12, is enriched in specific subsets of the CEM neurons. 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, suggesting that each receptor acts in a non-redundant manner in discrete olfactory neurons. Together, our results suggest that the evolutionarily distinct GPCRs SRW-97 and DMSR-12 act to facilitate male-specific sensation of ascr#8 through discrete subsets of CEM neurons.Competing Interest StatementThe authors have declared no competing interest.