microRNA miR-8 is a conserved negative regulator of Wnt signaling

• Published in: Proceedings of the National Academy of Sciences - PNAS 2008-10, Vol.105 (40), p.15417-15422
• Main Authors: Kennell, Jennifer A, Gerin, Isabelle, MacDougald, Ormond A, Cadigan, Ken M
• Format: Article
• Language: English
• Subjects: Adipocytes; Adipogenesis; Animals; Base Sequence; Biological Sciences; Cell culture techniques; Cell lines; Cells; compound eyes; Drosophila; Drosophila - metabolism; Drosophila Proteins - antagonists & inhibitors; Drosophila Proteins - metabolism; Drosophila pseudoobscura; Gene expression; Gene expression regulation; Genetics; imaginal discs; insect development; Insects; larvae; MicroRNA; MicroRNAs - genetics; MicroRNAs - metabolism; Molecular Sequence Data; Phenotypes; Proteins; Regulator genes; Ribonucleic acid; RNA; Signal Transduction; Stromal cells; Stromal Cells - metabolism; Three prime untranslated regions; wings; Wnt Proteins - antagonists & inhibitors; Wnt Proteins - genetics; Wnt Proteins - metabolism; Wnt signaling
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0807763105

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.