October 22, 2020

microRNA-dependent control of sensory neuron function regulates posture behaviour in Drosophila

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

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