Notch signaling regulates left-right asymmetry determination by inducing Nodal expression
Notch signaling regulates left-right asymmetry determination by inducing Nodal expression
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DOI：
10.1101/gad.1084703
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发表时间：
2003-05-15
影响因子：
10.5
通讯作者：
Gridley, T
中科院分区：
文献类型：
--
作者：
Krebs, LT;Iwai, N;Gridley, T
左右不对称的产生是脊椎动物身体计划建立的一个组成部分。在这里，我们表明Notch信号通路通过直接调节Nodal基因的表达在小鼠左右不对称的建立中起主要作用。Notch配体Dll 1的突变体或Notch 1和Notch 2受体的双重突变体的胚胎表现出左右不对称的多重缺陷。对调节节点特异性Nodal表达的增强子的分析揭示了RBP-J蛋白的结合位点的存在，RBP-J蛋白是Notch信号传导的主要转录介质。这些位点的突变破坏了该增强子在转基因小鼠中指导节点特异性基因表达的能力。我们的研究结果表明，Dll 1介导的Notch信号是必不可少的左右不对称的产生，和Notch途径的行为在Nodal表达的上游在小鼠左右不对称的决定。
Generation of left-right asymmetry is an integral part of the establishment of the vertebrate body plan. Here we show that the Notch signaling pathway plays a primary role in the establishment of left-right asymmetry in mice by directly regulating expression of the Nodal gene. Embryos mutant for the Notch ligand Dll1 or doubly mutant for the Notch1 and Notch2 receptors exhibit multiple defects in left-right asymmetry. Analysis of the enhancer regulating node-specific Nodal expression revealed the presence of binding sites for the RBP-J protein, the primary transcriptional mediator of Notch signaling. Mutation of these sites destroyed the ability of this enhancer to direct node-specific gene expression in transgenic mice. Our results demonstrate that Dll1-mediated Notch signaling is essential for generation of left-right asymmetry, and that the Notch pathway acts up-stream of Nodal expression during left-right asymmetry determination in mice.