A microRNA that controls the emergence of embryonic movement

Abstract

SUMMARYMovement is a key feature of animal systems, yet its embryonic origins are not fully understood. Here we investigate the genetic basis underlying the embryonic onset of movement inDrosophilafocusing on the role played by small non-coding RNAs (microRNAs, miRNAs). To this end, we first develop a quantitative behavioural pipeline capable of tracking embryonic movement in large populations of fly embryos, and using this system, discover that theDrosophilamiRNAmiR-2b-1plays a role in the emergence of movement. Through the combination of spectral analysis of embryonic motor patterns, cell sorting and RNAin situs, genetic reconstitution tests, and neural optical imaging we define thatmiR-2b-1influences the emergence of embryonic movement by exerting actions in the developing nervous system. Furthermore, through the combination of bioinformatics coupled to genetic manipulation of miRNA expression and phenocopy tests we identify a previously uncharacterised (but evolutionarily conserved) chloride channel encoding gene – which we termJanus– as a genetic target that mechanistically linksmiR-2b-1to the onset of movement. Cell-specific genetic reconstitution ofmiR-2b-1expression in a null miRNA mutant background, followed by behavioural assays and target gene analyses, suggest thatmiR-2b-1affects the emergence of movement through effects in sensory elements of the embryonic circuitry, rather than in the motor domain. Our work thus reports the first miRNA system capable of regulating embryonic movement, suggesting that other miRNAs are likely to play a role in this key developmental process inDrosophilaas well as in other species.