Generation of robust left-right asymmetry in the mouse embryo requires a self-enhancement and lateral-inhibition system
Generation of robust left-right asymmetry in the mouse embryo requires a self-enhancement and lateral-inhibition system
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DOI：
10.1016/j.devcel.2006.08.002
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发表时间：
2006-10-01
影响因子：
11.8
通讯作者：
Hamada, Hiroshi
中科院分区：
文献类型：
--
作者：
Nakamura, Tetsuya;Mine, Naoki;Hamada, Hiroshi
小鼠胚胎的两侧对称性被结节内向左流动的液体打破。然而，目前尚不清楚这种定向流动是如何转化为强大的、左侧特异的Nodal基因表达的，该基因表达决定并协调整个胚胎的左右部位。在操纵Nodal和Lefty基因表达时，我们观察到了一些现象，表明参与了自我增强和侧向抑制(SELI)系统。我们构建了一个数学SELI模型，该模型不仅可以模拟实验数据，还可以预测实验数据。正如模型预测的那样，节点表达即使在右侧也会启动。这些结果表明，定向流代表了胚胎左右两侧最初的微小差异，但不足以确定胚胎的位置。Nodeal和Lefty被部署为SELI系统，需要放大这种初始偏差并将其转换为稳健的不对称。
The bilateral symmetry of the mouse embryo is broken by leftward fluid flow in the node. However, it is unclear how this directional flow is then translated into the robust, left side-specific Nodal gene expression that determines and coordinates left-right situs throughout the embryo. While manipulating Nodal and Lefty gene expression, we have observed phenomena that are indicative of the involvement of a self-enhancement and lateral-inhibition (SELI) system. We constructed a mathematical SELI model that not only simulates, but also predicts, experimental data. As predicted by the model, Nodal expression initiates even on the right side. These results indicate that directional flow represents an initial small difference between the left and right sides of the embryo, but is insufficient to determine embryonic situs. Nodal and Lefty are deployed as a SELI system required to amplify this initial bias and convert it into robust asymmetry.