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Dev Biol. 2011 Sep 15;357(2):463-77. doi: 10.1016/j.ydbio.2011.07.014. Epub 2011 Jul 20.

miR-196 regulates axial patterning and pectoral appendage initiation.

Author information

1
Institute of Neuroscience, University of Oregon, Eugene, OR 97403, USA. xhe@uoneuro.uoregon.edu

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.

PMID:
21787766
PMCID:
PMC3164755
DOI:
10.1016/j.ydbio.2011.07.014
[Indexed for MEDLINE]
Free PMC Article

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