miR-263b controls circadian rhythms and structural plasticity of small ventral lateral neurons by inhibition of Beadex

Circadian clocks drive rhythmic physiology and behavior to allow adaption to daily environmental changes. In Drosophila, the small ventral lateral neurons (sLNvs) are the master pacemakers that control circadian rhythms. Circadian changes are observed in the dorsal axonal projections of the sLNvs, but their physiological importance and the underlying mechanism are unclear. Here we identified miR-263b as an important regulator of circadian rhythms in Drosophila. Flies depleted of miR-263b (miR-263bKO) exhibited dramatically impaired rhythms under constant darkness. Indeed, miR-263b is rhythmically expressed and controls circadian output by affecting the structural plasticity of sLNvs through inhibition of expression of the LIM-only protein Beadex (Bx). The misexpression of Bx in flies phenocopied miR-263bKO in behavior and molecular characteristics. In addition, the circadian phenotypes of miR-263bKO were recapitulated by mutating the miR-263b binding sites in the Bx 3'UTR. Together, these results establish miR-263b as an important regulator of circadian locomotor behavior.