title: Mesodermally expressed Drosophila microRNA-1 is regulated by Twist and is required in muscles during larval growth.
abstract: Although hundreds of evolutionarily conserved microRNAs have been discovered, the functions of most remain unknown. Here, we describe the embryonic spatiotemporal expression profile, transcriptional regulation, and loss-of-function phenotype of Drosophila miR-1 (DmiR-1). DmiR-1 RNA is highly expressed throughout the mesoderm of early embryos and subsequently in somatic, visceral, and pharyngeal muscles, and the dorsal vessel. The expression of DmiR-1 is controlled by the Twist and Mef2 transcription factors. DmiR-1KO mutants, generated using ends-in gene targeting, die as small, immobilized second instar larvae with severely deformed musculature. This lethality is rescued when a DmiR-1 transgene is expressed specifically in the mesoderm and muscle. Strikingly, feeding triggers DmiR-1KO-associated paralysis and death; starved first instar DmiR-1KO larvae are essentially normal. Thus, DmiR-1 is not required for the formation or physiological function of the larval musculature, but is required for the dramatic post-mitotic growth of larval muscle.
authors.affiliation: Department of Genetics, Dartmouth Medical School, Hanover, New Hampshire 03755, USA. nicholas.sokol@dartmouth.edu
authors.forename: Nicholas S
authors.initials: NS
authors.lastname: Sokol
authors.forename: Victor
authors.initials: V
authors.lastname: Ambros
mesh_terms: D000818:Animals; D004330:Drosophila; D029721:Drosophila Proteins / Q000378:metabolism*; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D007814:Larva / Q000254:growth & development; D008648:Mesoderm / Q000378:metabolism*; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D008938:Mitosis / Q000502:physiology; D024510:Muscle Development / Q000502:physiology*; D009132:Muscles / Q000196:embryology; D018006:Myogenic Regulatory Factors / Q000378:metabolism; D014158:Transcription, Genetic / Q000502:physiology
chemical_list: D029721:Drosophila Proteins; C499409:Mef2 protein, Drosophila; D035683:MicroRNAs; D018006:Myogenic Regulatory Factors