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心脏发育过程中 N-钙黏蛋白-连环蛋白复合体的需求。

Requirement for N-cadherin-catenin complex in heart development.

机构信息

Іnstitute of Molecular Biology and Genetic, Kyiv, Ukraine.

出版信息

Exp Biol Med (Maywood). 2011 Jul;236(7):816-22. doi: 10.1258/ebm.2011.010362. Epub 2011 Jun 16.

Abstract

Cell adhesion, mediated by N-cadherin, is critical for embryogenesis since N-cadherin-null embryos die during mid-gestation with multiple developmental defects. To investigate the role of N-cadherin in heart muscle development, N-cadherin was specifically deleted from myocardial cells in mice. The structural integrity of the myocardial cell wall was compromised in the N-cadherin mutant embryos, leading to a malformed heart and a delay in embryonic development. In contrast, cardiac-specific deletion of αE-catenin, found in adherens junctions, or β-catenin, did not cause any morphological defects in the embryonic heart, presumably due to compensation by αT-catenin that is normally found in intercalated disks and γ-catenin (plakoglobin), respectively. Embryos lacking β-catenin in the heart also exhibited a cardiac defect, but only later in development resulting in partial lethality. These genetic studies underscore the importance of the N-cadherin/catenin complex in cardiogenesis.

摘要

细胞黏附,由 N-钙黏蛋白介导,对于胚胎发生至关重要,因为 N-钙黏蛋白缺失的胚胎会在中期妊娠时死亡,并伴有多种发育缺陷。为了研究 N-钙黏蛋白在心肌发育中的作用,我们在小鼠的心肌细胞中特异性地删除了 N-钙黏蛋白。在 N-钙黏蛋白突变胚胎中,心肌细胞壁的结构完整性受到损害,导致心脏畸形和胚胎发育延迟。相比之下,黏着连接中的αE-连环蛋白或β-连环蛋白的心脏特异性缺失不会导致胚胎心脏出现任何形态缺陷,这可能是由于αT-连环蛋白(通常存在于闰盘)和γ-连环蛋白(桥粒斑蛋白)的代偿作用。心脏中缺乏β-连环蛋白的胚胎也表现出心脏缺陷,但仅在后期发育中发生,导致部分致死性。这些遗传研究强调了 N-钙黏蛋白/连环蛋白复合物在心脏发生中的重要性。

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