A gap junction connexin is required in the vertebrate left-right organizer
A gap junction connexin is required in the vertebrate left-right organizer
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DOI：
10.1016/j.ydbio.2009.09.035
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发表时间：
2009-12-15
影响因子：
2.7
通讯作者：
Johnson, Ross G.
中科院分区：
文献类型：
--
作者：
Hatler, Julia M.;Essner, Jeffrey J.;Johnson, Ross G.
脊椎动物胚胎的早期模式化涉及在左右（I-R）轴上产生不对称信号，这些信号定位并需要内部器官的正常功能。这种模式是由胚胎左侧的保守的节点/左侧信号级联引导的，被认为是由纤毛跳动不对称地引导的，纤毛跳动在哺乳动物节点和Kupffer囊泡（KV）（斑马鱼中的相关结构）中产生非对称流体流动。在Cx43.4的吗啉代敲低后，不对称基因表达和全局器官分布是随机的，与KV中Cx43.4的表达一致。在嵌合体胚胎中，Cx43.4优先在KV细胞中耗尽，这表明Cx43.4是KV中适当的L-R轴形成所特别需要的。在Cx43.4缺陷的胚胎的偏侧异常的机械基础是一个主要的形态发生缺陷，在KV管腔形成。此外，Cx43.4的作用似乎是保守的，因为它的直系同源物，人类Cx45，能够在L-R模式化过程中功能性地补偿斑马鱼Cx43.4。这是第一个报告连接蛋白功能的纤毛，淋巴结样细胞的IN与正常的L-R轴的发展。(C)2009 Elsevier Inc. All rights reserved.
Early patterning of vertebrate embryos involves the generation of asymmetric signals across the left-right (I-R) axis that position and are required for the proper function of internal organs. This patterning is directed by a conserved nodal/lefty signaling cascade on the left side of the embryo, thought to be asymmetrically directed by ciliary beating that generates a leftward fluid flow in the mammalian node and in Kupffer's vesicle (KV), the related structure in zebrafish. Following morpholino knockdown of Cx43.4, asymmetric gene expression and global organ distribution are randomized, consistent with the expression of Cx43.4 in KV. Randomization is recapitulated in mosaic embryos in which Cx43.4 is depleted preferentially in KV cells, showing that Cx43.4 is specifically required in KV for proper L-R axis formation. The mechanistic basis for the laterality anomalies in Cx43.4-deficient embryos is a primary morphogenesis defect during lumen formation in KV. Additionally, the role of Cx43.4 appears to be conserved given that its ortholog, human Cx45, is able to functionally compensate for zebrafish Cx43.4 during L-R patterning. This is the first report linking connexin function in the ciliated, node-like cells of IN with normal L-R axis development. (C) 2009 Elsevier Inc. All rights reserved.