Institute of Neuroscience, University of Oregon, Eugene, OR 97403, USA.
Dev Biol. 2011 Sep 15;357(2):463-77. doi: 10.1016/j.ydbio.2011.07.014. Epub 2011 Jul 20.
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.
脊椎动物 Hox 簇包含调节身体轴发育的蛋白质编码基因和微 RNA (miRNA) 基因，其功能尚不清楚。我们在斑马鱼胚胎中过表达了 Hox 簇 miRNA miR-196，发现了四个特定的、可行的表型：胸鳍芽起始失败、第 6 咽弓缺失、同源异形异常和颅椎丢失，以及肋骨和体节数量减少。相反，miR-196 的敲低会引起额外的咽弓、额外的肋骨和额外的体节，证实了 miR-196 的内源性作用。miR-196 的注射改变了 hox 基因的表达和通过视黄酸受体基因 rarab 的视黄酸信号。下调 rarab 模拟了 miR-196 过表达的胸鳍表型，并且在组织培养和胚胎中测试的报告构建体表明 rarab 3'UTR 是胸鳍芽起始的 miR-196 靶标。这些结果表明，Hox 簇 miRNA 调节与附近蛋白质编码 Hox 基因相似的轴向模式形成，并通过调节视黄酸信号至少部分作用于附肢模式形成。
