ZFIN ID: ZDB-PUB-110803-10
miR-196 regulates axial patterning and pectoral appendage initiation
He, X., Yan, Y.L., Eberhart, J.K., Herpin, A., Wagner, T.U., Schartl, M., and Postlethwait, J.H.
Date: 2011
Source: Developmental Biology   357(2): 463-77 (Journal)
Registered Authors: Eberhart, Johann, He, Xinjun, Postlethwait, John H., Schartl, Manfred, Wagner, Toni, Yan, Yi-Lin
Keywords: microRNA (miRNA), Mir196 (miR-196), axial skeletal patterning, pectoral fin, pharyngeal arch, retinoic acid
MeSH Terms:
  • Animal Fins/embryology*
  • Animal Fins/metabolism
  • Animals
  • Base Sequence
  • Body Patterning/genetics*
  • Bone and Bones/embryology
  • Bone and Bones/metabolism
  • Branchial Region/embryology
  • Branchial Region/metabolism
  • Embryo, Nonmammalian/metabolism
  • Gene Expression Regulation, Developmental
  • Genomics
  • Homeodomain Proteins/genetics
  • Homeodomain Proteins/metabolism
  • MicroRNAs/genetics
  • MicroRNAs/metabolism*
  • Molecular Sequence Data
  • Signal Transduction/genetics
  • Tretinoin/metabolism
  • Zebrafish/embryology*
  • Zebrafish/genetics*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed: 21787766 Full text @ Dev. Biol.
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 32UTR 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.