title: The microRNA miR-8 is a conserved negative regulator of Wnt signaling.
abstract: Wnt signaling plays many important roles in animal development. This evolutionarily conserved signaling pathway is highly regulated at all levels. To identify regulators of the Wnt/Wingless (Wg) pathway, we performed a genetic screen in Drosophila. We identified the microRNA miR-8 as an inhibitor of Wg signaling. Expression of miR-8 potently antagonizes Wg signaling in vivo, in part by directly targeting wntless, a gene required for Wg secretion. In addition, miR-8 inhibits the pathway downstream of the Wg signal by repressing TCF protein levels. Another positive regulator of the pathway, CG32767, is also targeted by miR-8. Our data suggest that miR-8 potently antagonizes the Wg pathway at multiple levels, from secretion of the ligand to transcription of target genes. In addition, mammalian homologues of miR-8 promote adipogenesis of marrow stromal cells by inhibiting Wnt signaling. These findings indicate that miR-8 family members play an evolutionarily conserved role in regulating the Wnt signaling pathway.
authors.affiliation: Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI 48109-1048, USA.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Kennell
authors.forename: Isabelle
authors.initials: I
authors.lastname: Gerin
authors.forename: Ormond A
authors.initials: OA
authors.lastname: MacDougald
authors.forename: Ken M
authors.initials: KM
authors.lastname: Cadigan
mesh_terms: D050156:Adipogenesis; D000818:Animals; D001483:Base Sequence; D004330:Drosophila / Q000378:metabolism; D029721:Drosophila Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D015398:Signal Transduction; D017154:Stromal Cells / Q000378:metabolism; D051153:Wnt Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; D035683:MicroRNAs; D051153:Wnt Proteins; C526630:MIRN8 microRNA, Drosophila