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

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...

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Bibliographic Details
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
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Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0807763105