N-cadherin is required for neural crest remodeling of the cardiac outflow tract
N-cadherin is required for neural crest remodeling of the cardiac outflow tract
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DOI：
10.1016/j.ydbio.2006.09.003
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发表时间：
2006-11-15
影响因子：
2.7
通讯作者：
Radice, Glenn L.
中科院分区：
文献类型：
--
作者：
Luo, Yang;High, Frances A.;Radice, Glenn L.
心脏神经嵴细胞在流出道主动脉肺隔形成过程中经历了广泛的细胞重排。然而，涉及这一基本过程的形态发生机制仍然知之甚少。为了确定Ca2+依赖性细胞粘附分子N-cadherin在小鼠神经嵴中的功能，我们应用Cre/loxP系统，建立了N-cadherin的小鼠胚胎遗传镶嵌。具体来说，神经嵴细胞中n -钙粘蛋白的缺失导致胚胎死亡，并伴有明显的心血管缺陷。神经嵴细胞迁移和归巢到心脏流出道生态位不受n -钙粘蛋白缺失的影响。然而，缺乏n-钙粘蛋白的神经嵴细胞无法经历与流出道重构相关的正常形态发生变化，导致大多数突变胚胎的动脉干持续存在。其他突变胚胎引发主动脉-肺隔形成；然而，神经嵴细胞不能沿着中线伸长和排列，保持圆形，与邻近细胞接触有限。有趣的是，在这些突变体中流出道的旋转是不完全的，这表明通道的排列依赖于n-钙粘蛋白产生的细胞骨架力。第二种心脏表型被观察到，在心外膜中n -钙粘蛋白的缺失导致心外膜和心肌之间异型细胞相互作用的破坏，导致心室心肌变薄。因此，我们得出结论，除了在心肌细胞粘附中发挥作用外，n -钙粘蛋白在神经嵴细胞重排中也是必需的，这对心脏流出道的形成和维持心外膜-心肌细胞相互作用至关重要。(c) 2006爱思唯尔公司版权所有。
Cardiac neural crest cells undergo extensive cell rearrangements during the formation of the aorticopulmonary septum in the outflow tract. However, the morphogenetic mechanisms involved in this fundamental process remain poorly understood. To determine the function of the Ca2+-dependent cell adhesion molecule, N-cadherin, in murine neural crest, we applied the Cre/loxP system and created mouse embryos genetically mosaic for N-cadherin. Specifically, deletion of N-cadherin in neural crest cells led to embryonic lethality with distinct cardiovascular defects. Neural crest cell migration and homing to the cardiac outflow tract niche were unaffected by loss of N-cadherin. However, N-cadherin-deficient neural crest cells were unable to undergo the normal morphogenetic changes associated with outflow tract remodeling, resulting in persistent truncus arteriosus in the majority of mutant embryos. Other mutant embryos initiated aorticopulmonary septum formation; however, the neural crest cells were unable to elongate and align properly along the midline and remained rounded with limited contact with their neighbors. Interestingly, rotation of the outflow tract was incomplete in these mutants suggesting that alignment of the channels is dependent on N-cadherin-generated cytoskeletal forces. A second cardiac phenotype was observed where loss of N-cadherin in the epicardium led to disruption of heterotypic cell interactions between the epicardium and myocardium resulting in a thinned ventricular myocardium. Thus, we conclude that in addition to its role in myocardial cell adhesion, N-cadherin is required for neural crest cell rearrangements critical for patterning of the cardiac outflow tract and in the maintenance of epicardial-myocardial cell interactions. (c) 2006 Elsevier Inc. All rights reserved.