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流体流动和相互关联的反馈回路建立了 Cerl2 mRNA 的左右不对称衰减。

Fluid flow and interlinked feedback loops establish left-right asymmetric decay of Cerl2 mRNA.

机构信息

Developmental Genetics Group, Graduate School of Frontier Biosciences, Osaka University, Suita 565-0871, Japan.

出版信息

Nat Commun. 2012;3:1322. doi: 10.1038/ncomms2319.

Abstract

Breaking of left-right symmetry in mouse embryos requires fluid flow at the node, but the precise action of the flow has remained unknown. Here we show that the left-right asymmetry of Cerl2 expression around the node, a target of the flow, is determined post-transcriptionally by decay of Cerl2 mRNA in a manner dependent on its 3' untranslated region. Cerl2 mRNA is absent specifically from the apical region of crown cells on the left side of the node. Preferential decay of Cerl2 mRNA on the left is initiated by the leftward flow and further enhanced by the operation of Wnt-Cerl2 interlinked feedback loops, in which Wnt3 upregulates Wnt3 expression and promotes Cerl2 mRNA decay, whereas Cerl2 promotes Wnt degradation. Mathematical modelling and experimental data suggest that these feedback loops behave as a bistable switch that can amplify in a noise-resistant manner a small bias conferred by fluid flow.

摘要

在小鼠胚胎中,左右对称性的破坏需要在节点处存在流体流动,但流动的确切作用仍不清楚。在这里,我们表明,在节点周围 Cerl2 表达的左右不对称性是通过 Cerl2 mRNA 的转录后降解来决定的,这种方式依赖于其 3'非翻译区。Cerl2 mRNA 特异性地从节点左侧冠细胞的顶端区域缺失。由左向右的流动引发了 Cerl2 mRNA 在左侧的优先降解,并且 Wnt-Cerl2 相互关联的反馈环的作用进一步增强了这种降解,其中 Wnt3 上调了 Wnt3 的表达并促进了 Cerl2 mRNA 的降解,而 Cerl2 则促进了 Wnt 的降解。数学建模和实验数据表明,这些反馈环表现为双稳态开关,可在抗噪的情况下以流体流动赋予的小偏差的方式进行放大。

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