miR-204 is required for lens and retinal development via Meis2 targeting
miR-204 is required for lens and retinal development via Meis2 targeting
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DOI：
10.1073/pnas.0914785107
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发表时间：
2010-08-31
影响因子：
11.1
通讯作者：
Banfi, Sandro
中科院分区：
文献类型：
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作者：
Conte, Ivan;Carrella, Sabrina;Banfi, Sandro
microRNAs（miRNAs）是一类在基因表达调控中起重要作用的非编码小分子RNA。然而，个体miRNAs在控制脊椎动物眼睛发育中的作用在很大程度上仍未被探索。在这里，我们表明，一个单一的miRNA，miR-204，调节青鳉鱼（Oryzias latipes）眼睛发育的多个方面。吗啉代介导的miR-204表达的消融导致以小眼球、异常透镜形成和视网膜的改变的背腹侧（D-V）图案为特征的眼表型，其与视裂缺损相关。使用多种体内和体外方法，我们鉴定了转录因子Meis 2作为miR-204功能的主要靶标之一。我们发现，与Pax 6通路的调节改变一起，由miR-204失活引起的Meis 2水平异常升高在很大程度上是观察到的表型的原因。这些数据提供了一个特定的miRNA如何调节眼睛形成中的多个事件的例子;同时，它们揭示了Meis 2在视网膜D-V图案化的规范中尚未报道的功能。
MicroRNAs (miRNAs) are small noncoding RNAs that have important roles in the regulation of gene expression. The roles of individual miRNAs in controlling vertebrate eye development remain, however, largely unexplored. Here, we show that a single miRNA, miR-204, regulates multiple aspects of eye development in the medaka fish (Oryzias latipes). Morpholino-mediated ablation of miR-204 expression resulted in an eye phenotype characterized by microphthalmia, abnormal lens formation, and altered dorsoventral (D-V) patterning of the retina, which is associated with optic fissure coloboma. Using a variety of in vivo and in vitro approaches, we identified the transcription factor Meis2 as one of the main targets of miR-204 function. We show that, together with altered regulation of the Pax6 pathway, the abnormally elevated levels of Meis2 resulting from miR-204 inactivation are largely responsible for the observed phenotype. These data provide an example of how a specific miRNA can regulate multiple events in eye formation; at the same time, they uncover an as yet unreported function of Meis2 in the specification of D-V patterning of the retina.