RNA-Processing Genes Control Sensory Neuron Function In Drosophila Melanogaster

The goal of this study was to identify genes involved in regulating the function of class IV multidendritic neurons (nociceptors) integral to the detection of thermal, mechanical, and photic stimuli. We used Drosophila melanogaster larvae as a model organism, which exhibit a distinct and quantifiable response to noxious stimuli termed nocifensive escape locomotion (NEL). We systematically knocked down putative RNA-processing genes with a previously identified role in dendrite development and/or alternative splicing by crossing a ppk-GAL4;UAS-dicer2 fly strain with RNAi lines targeting genes of interest. Using ppk as our driver limits expression to nociceptors and dicer2 promotes increased expression of RNAi transcripts. We then tested progeny for changes in nocifensive response latency relative to wild-type larvae using a thermal nociception assay. Twenty-five genes were identified for which knockdown resulted in either a significant increase or decrease in response latency, indicating a potential defect. Follow-up assays validated seven genes with an insensitive phenotype and two with a hypersensitive phenotype. Additionally, our results have confirmed that behavioral defects do not correlate with defects in dendrite morphology. Finally, a complex role for translation initiation factors was revealed, suggesting the potential for a nociception-specific and possibly IRES-mediated translation mechanism involving eIFG2 and eIF4E3