title: The microRNA miR-196 acts upstream of Hoxb8 and Shh in limb development.
abstract: 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.
authors.affiliation: Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.
authors.forename: Eran
authors.initials: E
authors.lastname: Hornstein
authors.forename: Jennifer H
authors.initials: JH
authors.lastname: Mansfield
authors.forename: Soraya
authors.initials: S
authors.lastname: Yekta
authors.forename: Jimmy Kuang-Hsien
authors.initials: JK
authors.lastname: Hu
authors.forename: Brian D
authors.initials: BD
authors.lastname: Harfe
authors.forename: Michael T
authors.initials: MT
authors.lastname: McManus
authors.forename: Scott
authors.initials: S
authors.lastname: Baskerville
authors.forename: David P
authors.initials: DP
authors.lastname: Bartel
authors.forename: Clifford J
authors.initials: CJ
authors.lastname: Tabin
mesh_terms: D000818:Animals; D001483:Base Sequence; D002642:Chick Embryo; D015536:Down-Regulation / Q000187:drug effects; D005121:Extremities / Q000196:embryology*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000235:genetics*; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009928:Organ Specificity; D043244:Ribonuclease III / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects / Q000235:genetics; D014212:Tretinoin / Q000494:pharmacology
chemical_list: D053823:Hedgehog Proteins; D018398:Homeodomain Proteins; C095822:Hoxb8 protein, mouse; D035683:MicroRNAs; C465570:Shh protein, mouse; D015534:Trans-Activators; D014212:Tretinoin; D043244:Ribonuclease III