The microRNA miR-196 acts upstream of Hoxb8 and Shh in limb development

• Published in: Nature Vol. 438; no. 7068; pp. 671 - 674
• Main Authors: Hornstein, Eran, Harfe, Brian D, Tabin, Clifford J, Mansfield, Jennifer H, Hu, Jimmy Kuang-Hsien, McManus, Michael T, Yekta, Soraya, Bartel, David P, Baskerville, Scott
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 01.12.2005; Nature Publishing Group
• Subjects: Anatomy & physiology; Animals; Base Sequence; Biological and medical sciences; Chick Embryo; Down-Regulation - drug effects; Embryology: invertebrates and vertebrates. Teratology; Extremities - embryology; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation, Developmental - drug effects; Gene Expression Regulation, Developmental - genetics; Genes; Hedgehog Proteins; Homeodomain Proteins - genetics; Homeodomain Proteins - metabolism; Mice; MicroRNAs - genetics; MicroRNAs - metabolism; Molecular embryology; Organ Specificity; Ribonuclease III - metabolism; Ribonucleic acid; RNA; Rodents; Trans-Activators - genetics; Trans-Activators - metabolism; Transcription, Genetic - drug effects; Transcription, Genetic - genetics; Tretinoin - pharmacology; Vertebrates; Vertebrata; Regulation(control); Mammalia; Coordination; Gene; RNA; Mouse; Transcription; Limb; Rodentia; Development
• ISSN: 0028-0836; 1476-4687; 1476-4679
• DOI: 10.1038/nature04138

MicroRNAs (miRNAs) are an abundant class of gene regulatory molecules (reviewed in refs 1, 2). Although computational work indicates that miRNAs repress more than a third of human genes, their roles in vertebrate development are only now beginning to be determined. Here we show that miR-196 acts upstream of Hoxb8 and Sonic hedgehog (Shh) in vivo in the context of limb development, thereby identifying a previously observed but uncharacterized inhibitory activity that operates specifically in the hindlimb. Our data indicate that miR-196 functions in a fail-safe mechanism to assure the fidelity of expression domains that are primarily regulated at the transcriptional level, supporting the idea that many vertebrate miRNAs may function as a secondary level of gene regulation.