title: miR-124 Regulates Diverse Aspects of Rhythmic Behavior in Drosophila.
abstract: Circadian clocks enable organisms to anticipate and adapt to fluctuating environmental conditions. Despite substantial knowledge of central clock machineries, we have less understanding of how the central clock's behavioral outputs are regulated. Here, we identify Drosophila miR-124 as a critical regulator of diurnal activity. During normal light/dark cycles, mir-124 mutants exhibit profoundly abnormal locomotor activity profiles, including loss of anticipatory capacities at morning and evening transitions. Moreover,mir-124 mutants exhibited striking behavioral alterations in constant darkness (DD), including a temporal advance in peak activity. Nevertheless, anatomical and functional tests demonstrate a normal circadian pacemaker in mir-124 mutants, indicating this miRNA regulates clock output. Among the extensive miR-124 target network, heterozygosity for targets in the BMP pathway substantially corrected the evening activity phase shift in DD. Thus, excess BMP signaling drives specific circadian behavioral output defects in mir-124 knock-outs.
  
  
  CONCLUSIONS
  Circadian clocks control rhythmic behaviors of most life-forms. Despite extensive knowledge of the central clock, there is less understanding of how its behavioral outputs are regulated. Here, we identify a conserved neural microRNA as a critical regulator of diurnal behavior. We find Drosophila mir-124 mutants exhibit robust activity abnormalities during normal light/dark cycles and during constant darkness. Nevertheless, as the central pacemaker is functional in these mutants, miR-124 regulates clock output. We provide mechanistic insight by showing deregulation of miR-124 targets in BMP signaling drives specific mir-124 defects. In summary,Drosophila mir-124 mutants reveal post-transcriptional control of circadian activities, and impact of BMP signaling in behavioral output.
authors.affiliation: Sloan-Kettering Institute, Department of Developmental Biology, New York, New York 10065.
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Garaulet
authors.affiliation: Sloan-Kettering Institute, Department of Developmental Biology, New York, New York 10065, Neuroscience Program, Weill Graduate School of Medical Sciences, Cornell University, New York, New York 10065.
authors.forename: Kailiang
authors.initials: K
authors.lastname: Sun
authors.affiliation: Laboratory of Genetics, The Rockefeller University, New York, New York 10065, and.
authors.forename: Wanhe
authors.initials: W
authors.lastname: Li
authors.affiliation: Sloan-Kettering Institute, Department of Developmental Biology, New York, New York 10065.
authors.forename: Jiayu
authors.initials: J
authors.lastname: Wen
authors.affiliation: Sloan-Kettering Institute, Department of Developmental Biology, New York, New York 10065.
authors.forename: Alexandra M
authors.initials: AM
authors.lastname: Panzarino
authors.affiliation: Laboratory of Genetics, The Rockefeller University, New York, New York 10065, and.
authors.forename: Jenna L
authors.initials: JL
authors.lastname: O'Neil
authors.affiliation: Institute for Biology, Freie Universitaet Berlin, 14195 Berlin, Germany.
authors.forename: P Robin
authors.initials: PR
authors.lastname: Hiesinger
authors.affiliation: Laboratory of Genetics, The Rockefeller University, New York, New York 10065, and.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Young
authors.affiliation: Sloan-Kettering Institute, Department of Developmental Biology, New York, New York 10065, laie@mskcc.org.
authors.forename: Eric C
authors.initials: EC
authors.lastname: Lai
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D001683:Biological Clocks / Q000502:physiology*; D001921:Brain / Q000502:physiology*; D063226:Central Pattern Generators / Q000502:physiology*; D002940:Circadian Rhythm / Q000502:physiology*; D004330:Drosophila / Q000502:physiology*; D008124:Locomotion / Q000502:physiology*; D008297:Male; D035683:MicroRNAs / Q000502:physiology*
chemical_list: C572067:MIRN124 microRNA, Drosophila; D035683:MicroRNAs
keywords: BMP signaling; Drosophila; activity mode; activity phase; circadian rhythm; microRNA