Two nodal-responsive enhancers control left-right asymmetric expression of Nodal
Two nodal-responsive enhancers control left-right asymmetric expression of Nodal
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DOI：
10.1002/dvdy.20192
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发表时间：
2005-04-01
影响因子：
2.5
通讯作者：
Hamada, H
中科院分区：
文献类型：
--
作者：
Saijoh, Y;Oki, S;Hamada, H
Nodal在侧板中胚层（LPM）中的不对称表达在左右（L-R）模式中起主要作用。位于内含子1（ASE）的Nodal应答增强子调节Nodal的不对称表达，但尚不清楚Nodal表达如何在左LPM中启动。在此，我们在小鼠Nodal基因的上游区域鉴定了第二个不对称增强子（左侧特异性增强子，LSE）。LSE也位于人类NODAL的相应区域。LSE的L-R特异性受iv和inv突变的影响。LSE活性需要保守的FoxH 1结合序列，并且LSE活性依赖于Nodal辅助受体隐藏蛋白，这表明LSE被Nodal信号激活。然而，缺乏LSE的突变小鼠没有表现出明显的L-R图案化缺陷。这些结果表明，在左侧LPM中的Nodal表达是由两种Nodal应答性自身调节增强子ASE和LSE的组合诱导的。(c)2005 Wiley-Liss，Inc.
Asymmetric expression of Nodal in the lateral plate mesoderm (LPM) plays the major role in left-right (L-R) patterning. A Nodal-responsive enhancer located in the intron 1 (ASE) regulates asymmetric Nodal expression, but it is unknown how Nodal expression is initiated in the left LPM. Here, we have identified a second asymmetric enhancer (left side-specific enhancer, LSE) in the upstream region of mouse Nodal gene. LSE is also located in the corresponding region of human NODAL. L-R specificity of LSE is affected by iv and inv mutations. The requirement of a conserved FoxH1-binding sequence for LSE activity and the dependence of LSE activity on Nodal coreceptor Cryptic indicate that LSE is activated by Nodal signal. However, the mutant mouse lacking LSE does not show obvious L-R patterning defects. These results suggest that Nodal expression in the left LPM is induced by a combination of two Nodal-responsive autoregulatory enhancers, ASE and LSE. (c) 2005 Wiley-Liss, Inc.