Modulation of miR-210 alters phasing of circadian locomotor activity and impairs projections of PDF clock neurons in Drosophila melanogaster

摘要

Single microRNAs are usually associated with hundreds of putative target genes that can influence multiple phenotypic traits in Drosophila, ranging from development to behaviour. We investigated the function of Drosophila miR-210 in circadian behaviour by misexpressing it within circadian clock cells. Manipulation of miR-210 expression levels in the PDF (pigment dispersing factor) positive neurons affected the phase of locomotor activity, under both light-dark conditions and constant darkness. PER cyclical expression was not affected in clock neurons, however, when miR-210 was up-regulated, a dramatic alteration in the morphology of PDF ventral lateral neuron (LNv) arborisations was observed. The effect of miR-210 in shaping neuronal projections was confirmed in vitro , using a Drosophila neuronal cell line. A transcriptomic analysis revealed that miR-210 overexpression affects the expression of several genes belonging to pathways related to circadian processes, neuronal development, GTPases signal transduction and photoreception. Collectively, these data reveal the role of miR-210 in modulating circadian outputs in flies and guiding/remodelling PDF positive LNv arborisations and indicate that miR-210 may have pleiotropic effects on the clock, light perception and neuronal development. Author summary In recent years, the role of microRNAs in regulating the endogenous circadian clock and its rhythmic outputs for behaviour/physiology has been recognized. We have observed that depletion or over-expression of miR-210 in Drosophila melanogaster modulates the phase of locomotor activity, without affecting the molecular oscillation of the pacemaker neurons. Moreover, miR-210 over-expression dramatically alters the pattern of projections from the PDF-positive Lateral Neurons (LNvs). Differentially expressed genes detected in miR-210 over-expressing flies implicated circadian processes, neuronal development, and photoreception. Taken together, our findings indicate the involvement of miR-210 in modulating circadian output and remodelling the projections of PDF clock neurons, and suggest that miR-210 may have pleiotropic effects on clock, light perception and neuronal development.