Asymmetric distribution of dynamic calcium signals in the node of mouse embryo during left-right axis formation.
Asymmetric distribution of dynamic calcium signals in the node of mouse embryo during left-right axis formation.
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DOI：
10.1016/j.ydbio.2013.01.018
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发表时间：
2013-04
影响因子：
2.7
通讯作者：
Daisuke Takao;T. Nemoto;T. Abe;H. Kiyonari;H. Kajiura‐Kobayashi;Hidetaka Shiratori;S. Nonaka
中科院分区：
文献类型：
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作者：
Daisuke Takao;T. Nemoto;T. Abe;H. Kiyonari;H. Kajiura‐Kobayashi;Hidetaka Shiratori;S. Nonaka
在小鼠胚胎的淋巴结中，纤毛的旋转运动产生了一种称为淋巴结流的外部液体流，它决定了左右不对称的基因表达。结节流如何转化为不对称的基因表达仍有争议，但已提出在结节左侧内胚层细胞中Ca 2+水平的增加起作用。然而，尚未描述节点本身内部的Ca 2+信号。通过我们优化的Ca 2+成像方法，我们能够观察到活小鼠胚胎淋巴结中的动态Ca 2+信号。药理学干扰的Ca 2+信号不影响纤毛运动或结流量，但确实改变了Nodal和Cerl-2基因的表达模式。Ca 2+信号频率和分布的定量分析表明，在左-右轴的建立，以前对称的Ca 2+信号变得偏向左侧。在iv/iv突变体胚胎，表现出随机偏侧，由于纤毛不动，Ca 2+信号被发现是不同的左侧，右侧，或双边，因此平均对称。在Pkd 2突变体胚胎，缺乏多囊蛋白-2，Ca 2+渗透阳离子通道所需的左右轴的形成，Ca 2+信号频率低于野生型胚胎。我们的数据支持一个模型，其中节点中的动态Ca 2+信号参与左右图案。
In the node of mouse embryo, rotational movements of cilia generate an external liquid flow known as nodal flow, which determines left–right asymmetric gene expression. How nodal flow is converted into asymmetric gene expression is still controversial, but the increase of Ca2+levels in endodermal cells to the left of the node has been proposed to play a role. However, Ca2+signals inside the node itself have not yet been described. By our optimized Ca2+imaging method, we were able to observe dynamic Ca2+signals in the node in live mouse embryos. Pharmacological disruption of Ca2+signals did not affect ciliary movements or nodal flow, but did alter the expression patterns of the Nodal and Cerl-2 genes. Quantitative analyses of Ca2+signal frequencies and distributions showed that during left–right axis establishment, formerly symmetric Ca2+signals became biased to the left side. In iv/iv mutant embryos that showed randomized laterality due to ciliary immotility, Ca2+signals were found to be variously left-sided, right-sided, or bilateral, and thus symmetric on average. In Pkd2 mutant embryos, which lacked polycystin-2, a Ca2+-permeable cation channel necessary for left–right axis formation, the Ca2+signal frequency was lower than in wild-type embryos. Our data support a model in which dynamic Ca2+signals in the node are involved in left–right patterning.