title: miR-196 regulates axial patterning and pectoral appendage initiation.
abstract: Vertebrate Hox clusters contain protein-coding genes that regulate body axis development and microRNA (miRNA) genes whose functions are not yet well understood. We overexpressed the Hox cluster microRNA miR-196 in zebrafish embryos and found four specific, viable phenotypes: failure of pectoral fin bud initiation, deletion of the 6th pharyngeal arch, homeotic aberration and loss of rostral vertebrae, and reduced number of ribs and somites. Reciprocally, miR-196 knockdown evoked an extra pharyngeal arch, extra ribs, and extra somites, confirming endogenous roles of miR-196. miR-196 injection altered expression of hox genes and the signaling of retinoic acid through the retinoic acid receptor gene rarab. Knocking down rarab mimicked the pectoral fin phenotype of miR-196 overexpression, and reporter constructs tested in tissue culture and in embryos showed that the rarab 3'UTR is a miR-196 target for pectoral fin bud initiation. These results show that a Hox cluster microRNA modulates development of axial patterning similar to nearby protein-coding Hox genes, and acts on appendicular patterning at least in part by modulating retinoic acid signaling.
authors.affiliation: Institute of Neuroscience, University of Oregon, Eugene, OR 97403, USA. xhe@uoneuro.uoregon.edu
authors.forename: Xinjun
authors.initials: X
authors.lastname: He
authors.forename: Yi-Lin
authors.initials: YL
authors.lastname: Yan
authors.forename: Johann K
authors.initials: JK
authors.lastname: Eberhart
authors.forename: Amaury
authors.initials: A
authors.lastname: Herpin
authors.forename: Toni U
authors.initials: TU
authors.lastname: Wagner
authors.forename: Manfred
authors.initials: M
authors.lastname: Schartl
authors.forename: John H
authors.initials: JH
authors.lastname: Postlethwait
mesh_terms: D058500:Animal Fins / Q000196:embryology* / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D019521:Body Patterning / Q000235:genetics*; D001842:Bone and Bones / Q000196:embryology / Q000378:metabolism; D001934:Branchial Region / Q000196:embryology / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D023281:Genomics; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D015398:Signal Transduction / Q000235:genetics; D014212:Tretinoin / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D018398:Homeodomain Proteins; C561942:MIRN196 microRNA, zebrafish; D035683:MicroRNAs; D029961:Zebrafish Proteins; D014212:Tretinoin