The impact of microRNA regulation on adult Drosophila locomotion

Locomotion is a vital behaviour for animal survival allowing individuals to escape predators and find food or mates. The nervous system plays a critical role in regulating coordinated locomotion by integrating sensory inputs and directing output via groups of motor and command neurons. Despite the importance of locomotion, how the nervous system controls movement is not yet clear.

Here, we investigate this problem by studying the impact of the genetic system on the regulation of movement in the fruit fly Drosophila melanogaster, an excellent system to study gene function.

We focus on the roles of a recently discovered class of small non-coding RNA molecules termed microRNAs (miRNAs), which act as repressors of gene expression and show widespread impact on biological functions. Our general approach relies on using loss-of-function miRNA mutants to study the consequence of this perturbation on adult fly locomotion.

In particular, we develop a high-throughput behavioural pipeline and use it to identify several Drosophila miRNAs that are essential for normal adult locomotion. Our design compares the effects of miRNA knockout on motor function at two developmental stages and our results suggest distinct roles of miRNAs at different stages of the fly life cycle. To gain a mechanistic understanding, we select miR-278 for detailed analysis. We find that miR-278 mutants show significantly increased turning frequency and using a miR-278-specific reporter line, we identify the neuronal expression domain of this miRNA. We also find that manipulation of miR-278+ neuronal activity affects adult turning frequency suggesting that miR-278 might be regulating behaviour through modulation of neuronal activity.

Our study contributes to identifying the principles of miRNA-dependent locomotor control across Drosophila developmental stages and advances the understanding of the mechanisms by which miRNAs control neural function and behaviour.