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

Paola Cusumano,Cristiano De Pittà,Claudia Tregnago,Alberto Biscontin,Rodolfo Costa,Gabriella M Mazzotta,Federica Sandrelli,Paul H Taghert

doi:10.1371/journal.pgen.1007500

Paola Cusumano, Cristiano De Pittà + Show 6 more

Open Access

https://doi.org/10.1371/journal.pgen.1007500

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Journal: PLoS Genetics	Publication Date: Jul 16, 2018
Citations: 29	License type: CC BY 4.0

Affiliation: University of Padua

Abstract

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.

Highlights

Circadian oscillators consist of input pathways that receive external signals, such as light, temperature and food, a central pacemaker that generates rhythmicity, and output pathways that activate downstream rhythmic processes [1,2,3]
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
MiR-210 over-expression dramatically alters the pattern of projections from the Pigment Dispersing Factor (PDF)-positive Lateral Neurons (LNvs)

Summary

Introduction

Circadian oscillators consist of input pathways that receive external signals, such as light, temperature and food, a central pacemaker that generates rhythmicity, and output pathways that activate downstream rhythmic processes [1,2,3]. These internal timers allow organisms to adjust their physiology and behaviour to the most appropriate phases of the environmental 24 hour cycle imposed by the Earth’s rotation. Four out of five s-LNvs and the l-LNvs express Pigment Dispersing Factor (PDF), a neuropeptide which is involved in shaping locomotor activity in free-running conditions under constant darkness (DD). The s-LNvs are capable of driving dawn activity and sustaining rhythmicity under DD whereas a subset of LNds and the 5th s-LNv are responsible for dusk activity and for sustaining rhythmicity under LL [9,10,11]

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