Nociceptor-Enriched Genes Required for Normal Thermal Nociception

Here, we describe a targeted reverse genetic screen for thermal nociception genes in Drosophila larvae. Using laser capture microdissection and microarray analyses of nociceptive and non-nociceptive neurons, we identified 275 nociceptor-enriched genes. We then tested the function of the enriched genes with nociceptor-specific RNAi and thermal nociception assays. Tissue-specific RNAi targeted against 14 genes caused insensitive thermal nociception while targeting of 22 genes caused hypersensitive thermal nociception. Previously uncategorized genes were named for heat resistance (i.e., boilerman, fire dancer, oven mitt, trivet, thawb, and bunker gear) or heat sensitivity (firelighter, black match, eucalyptus, primacord, jet fuel, detonator, gasoline, smoke alarm, and jetboil). Insensitive nociception phenotypes were often associated with severely reduced branching of nociceptor neurites and hyperbranched dendrites were seen in two of the hypersensitive cases. Many genes that we identified are conserved in mammals. [Display omitted] •Laser capture microarray analyses identify 275 nociceptor-enriched genes•Nociceptor-specific RNAi screens implicate 36 genes in thermal nociception•The screens uncover genes affecting nociception signaling•Homologs of nociception genes are enriched in mammalian nociceptors Using tissue-specific microarray analyses and nociceptor-specific RNAi screens in Drosophila, Honjo et al. identify genes that both show enriched expression in nociceptors and are functionally important for thermal nociception. Many of genes uncovered by the screen are evolutionarily conserved.