miR-124 acts during Drosophila development to determine the phase of adult circadian behavior

Circadian behaviors need to be properly phased with the day/night cycle to be beneficial. We previously showed that the microRNA miR-124 regulates circadian behavior phase in Drosophila . Here, we report that miR-124 expression during larval development is required for proper phasing of both morning and evening peaks of activity in adults. Loss of miR-124 results in significant miswiring within the circadian neural network and severely alters neural activity rhythms in the ventral Lateral Neurons (s-LNvs) and the posterior Dorsal Neurons 1 (DN1ps), which control the timing of morning and evening activity. Silencing the s-LNvs in miR-124 mutant flies restores the phase of evening activity, while activating the DN1ps rescues the phases of both morning and evening activities. Our findings thus reveal the pivotal role of miR-124 in sculpting the circadian neural network during development and its long-lasting impact on circuit activity and adult circadian behavior.