N-cadherin relocalization during cardiac trabeculation
N-cadherin relocalization during cardiac trabeculation
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DOI：
10.1073/pnas.1606385113
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发表时间：
2016-07-05
影响因子：
11.1
通讯作者：
Stainier, Didier Y. R.
中科院分区：
文献类型：
--
作者：
Cherian, Anoop V.;Fukuda, Ryuichi;Stainier, Didier Y. R.
在心脏小梁形成过程中，心肌细胞从最外层（致密层）分层，形成称为小梁的复杂肌肉结构。当这些心肌细胞分层时，粘附连接的重塑必须紧密协调，这样细胞才能从致密层中挤出，同时保持与相邻细胞的紧密接触。在这项研究中，我们研究了N-钙粘蛋白（Cdh 2）在斑马鱼心脏小梁形成过程中的分布。通过分析在斑马鱼cdh 2启动子控制下表达的Cdh 2-EGFP融合蛋白的定位，我们最初观察到Cdh 2-EGFP表达沿着胚胎心肌细胞的侧面，以均匀分布的模式，偶尔出现斑点。在几个小时内，Cdh 2-EGFP在心肌细胞侧面的分布演变成一个清晰的点状图案，因为Cdh 2-EGFP分子在点状簇外增加了这些聚集体的大小。此外，Cdh 2-EGFP分子也出现在保持在致密层中的心肌细胞的基底侧。分层的心肌细胞在面向致密层心肌细胞的基底侧的表面上积累Cdh 2-EGFP，从而使这些层之间紧密粘附。重要的是，我们发现，血流/心肌收缩力是从Cdh 2-EGFP的均匀分布到斑点形成的过渡所必需的。此外，使用延时成像跳动的心脏与Cdh 2串联荧光蛋白定时器转基因线，我们观察到Cdh 2-EGFP分子似乎从心肌细胞的侧面移动到基底侧沿着细胞膜，和Erb-b2受体酪氨酸激酶2（Erbb 2）的功能是需要这种重新定位。
During cardiac trabeculation, cardiomyocytes delaminate from the outermost (compact) layer to form complex muscular structures known as trabeculae. As these cardiomyocytes delaminate, the remodeling of adhesion junctions must be tightly coordinated so cells can extrude from the compact layer while remaining in tight contact with their neighbors. In this study, we examined the distribution of N-cadherin (Cdh2) during cardiac trabeculation in zebrafish. By analyzing the localization of a Cdh2-EGFP fusion protein expressed under the control of the zebrafish cdh2 promoter, we initially observed Cdh2-EGFP expression along the lateral sides of embryonic cardiomyocytes, in an evenly distributed pattern, and with the occasional appearance of punctae. Within a few hours, Cdh2-EGFP distribution on the lateral sides of cardiomyocytes evolves into a clear punctate pattern as Cdh2-EGFP molecules outside the punctae cluster to increase the size of these aggregates. In addition, Cdh2-EGFP molecules also appear on the basal side of cardiomyocytes that remain in the compact layer. Delaminating cardiomyocytes accumulate Cdh2-EGFP on the surface facing the basal side of compact layer cardiomyocytes, thereby allowing tight adhesion between these layers. Importantly, we find that blood flow/cardiac contractility is required for the transition from an even distribution of Cdh2-EGFP to the formation of punctae. Furthermore, using time-lapse imaging of beating hearts in conjunction with a Cdh2 tandem fluorescent protein timer transgenic line, we observed that Cdh2-EGFP molecules appear to move from the lateral to the basal side of cardiomyocytes along the cell membrane, and that Erb-b2 receptor tyrosine kinase 2 (Erbb2) function is required for this relocalization.