All what we see, touch, hear, taste or smell must first be detected by the sensory elements in our nervous system. Sensory neurons, therefore, represent a critical component in all neural circuits and their correct function is essential for the generation of behaviour and adaptation to the environment. Here we report that a gene encoding the evolutionarily conserved microRNA (miRNA) miR-263b, plays a key behavioural role in Drosophila through effects on the function of larval sensory neurons. Several independent experiments support this finding. First, miRNA expression analysis by means of a miR-263b reporter line, and fluorescent-activated cell sorting coupled to quantitative PCR, both demonstrate expression of miR-263b in Drosophila larval sensory neurons. Second, behavioural tests in miR-263b null mutants show defects in self-righting: an innate and evolutionarily conserved posture control behaviour that allows the larva to return to its normal position if turned upside-down. Third, competitive inhibition of miR-263b in sensory neurons using a miR-263b sponge leads to self-righting defects. Fourth, systematic analysis of sensory neurons in miR-263b mutants shows no detectable morphological defects in their stereotypic pattern. Fifth, genetically-encoded calcium sensors expressed in the sensory domain reveal a reduction in neural activity in miR-263b null mutants. Sixth, miR-263b null mutants show a reduced touch-response behaviour and a compromised response to sound, both characteristic of larval sensory deficits. Furthermore, bioinformatic miRNA target analysis, gene expression assays, and behavioural phenocopy experiments suggest that miR-263b might exert its effects, at least in part, through repression of the bHLH transcription factor atonal. Altogether, our study suggests a model in which miRNA-dependent control of transcription factor expression affects sensory function and behaviour. Building on the evolutionary conservation of miR-263b, we propose that similar processes may modulate sensory function in other animals, including mammals.
bioRxiv Subject Collection: Neuroscience