Conserved requirement for EGF-CFC genes in vertebrate left-right axis formation
Conserved requirement for EGF-CFC genes in vertebrate left-right axis formation
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DOI：
10.1101/gad.13.19.2527
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发表时间：
1999-10-01
影响因子：
10.5
通讯作者：
Shen, MM
中科院分区：
文献类型：
--
作者：
Yan, YT;Gritsman, K;Shen, MM
脊椎动物胚胎中左右（L-R）轴的规范需要将位置信息从节点转移到外周，导致侧板中胚层中基因表达不对称。我们表明，这种激活的L-R侧不对称需要进化保守的活性的EGF-CFC家族的细胞外因子的成员。靶向破坏鼠隐藏蛋白导致L-R偏侧性缺陷，包括腹部位置随机化、脾功能减退和肺右异构，以及随机化的胚胎翻转和心脏成环。类似地，斑马鱼独眼针头（oep）突变体，已被部分拯救的mRNA注射显示异位，包括随机化的心脏循环和胰腺的位置。在隐藏和oep突变胚胎，L-R不对称表达的Nodal/cyclops，Lefty 2/antivin，和Pitx 2不发生在侧板中胚层，而在隐藏突变体Lefty 1表达是不存在的前景底板。值得注意的是，在隐性突变体中仍然观察到Nodal在节点的侧边缘处的L-R不对称表达，表明L-R特化发生在节点中而不是侧板中。结合先前的发现，oep是所需的节点信号在斑马鱼，我们建议，由Nodal和EGF-CFC活动介导的信号通路是必不可少的L-R的位置信息从节点的转移。
Specification of the left-right (L-R) axis in the vertebrate embryo requires transfer of positional information from the node to the periphery, resulting in asymmetric gene expression in the lateral plate mesoderm. We show that this activation of L-R lateral asymmetry requires the evolutionarily conserved activity of members of the EGF-CFC family of extracellular factors. Targeted disruption of murine Cryptic results in L-R laterality defects including randomization of abdominal situs, hyposplenia, and pulmonary right isomerism, as well as randomized embryo turning and cardiac looping. Similarly, zebrafish one-eyed pinhead (oep) mutants that have been rescued partially by mRNA injection display heterotaxia, including randomization of heart looping and pancreas location. In both Cryptic and oep mutant embryos, L-R asymmetric expression of Nodal/cyclops, Lefty2/antivin, and Pitx2 does not occur in the lateral plate mesoderm, while in Cryptic mutants Lefty1 expression is absent from the prospective floor plate. Notably, L-R asymmetric expression of Nodal at the lateral edges of the node is still observed in Cryptic mutants, indicating that L-R specification has occurred in the node but not the lateral plate. Combined with the previous finding that oep is required for nodal signaling in zebrafish, we propose that a signaling pathway mediated by Nodal and EGF-CFC activities is essential for transfer of L-R positional information from the node.