Fusion competence of myoblasts rendered genetically null for N-cadherin in culture
Fusion competence of myoblasts rendered genetically null for N-cadherin in culture
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DOI：
10.1083/jcb.138.2.331
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发表时间：
1997-07-28
影响因子：
7.8
通讯作者：
Blau, HM
中科院分区：
文献类型：
--
作者：
Charlton, CA;Mohler, WA;Blau, HM
成肌细胞融合对于肌肉组织发育是必不可少的，但仍然知之甚少。N-钙粘蛋白，像其他细胞表面粘附分子一样，已经被其他人基于其表达模式和抗体或肽模拟物对成肌细胞聚集和融合的抑制而涉及肌肉形成。使N-钙粘蛋白纯合无效的小鼠揭示了该分子在早期发育中的普遍重要性，但没有测试在骨骼肌发生中的作用，因为胚胎在肌肉形成之前就已经死亡。为了从遗传学上测试所提出的N-钙粘蛋白在成肌细胞融合中的作用，我们成功地在培养中获得了N-钙粘蛋白缺失的原代成肌细胞。发现表达或缺乏N-钙粘蛋白的成肌细胞的融合是等效的，无论是在体外通过lacZ的顺反子内互补还是在体内通过注射到成年小鼠的肌肉中。也排除了N-钙粘蛋白在介导碱性成纤维细胞生长因子的作用中的重要作用。这些从成人组织中获得遗传纯合的空体细胞的方法应该具有广泛的应用。在这里，它们清楚地表明，推定的融合分子，N-钙粘蛋白，是不是必不可少的成肌细胞融合。
Myoblast fusion is essential to muscle tissue development yet remains poorly understood, N-cadherin, like other cell surface adhesion molecules, has been implicated by others in muscle formation based on its pattern of expression and on inhibition of myoblast aggregation and fusion by antibodies or peptide mimics, Mice rendered homozygous null for N-cadherin revealed the general importance of the molecule in early development, but did not test a role in skeletal myogenesis, since the embryos died before muscle formation. To test genetically the proposed role of N-cadherin in myoblast fusion, we successfully obtained N-cadherin null primary myoblasts in culture, Fusion of myoblasts expressing or lacking N-cadherin was found to be equivalent, both in vitro by intracistronic complementation of lacZ and in vivo by injection into the muscles of adult mice. An essential role for N-cadherin in mediating the effects of basic fibroblast growth factor was also excluded. These methods for obtaining genetically homozygous null somatic cells from adult tissues should have broad applications, Here, they demonstrate clearly that the putative fusion molecule, N-cadherin, is not essential for myoblast fusion.