Radice G L, Rayburn H, Matsunami H, Knudsen K A, Takeichi M, Hynes R O
Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge 02139, USA.
Dev Biol. 1997 Jan 1;181(1):64-78. doi: 10.1006/dbio.1996.8443.
To investigate the functions of N-cadherin in vivo, we have mutated the gene encoding this adhesion protein in mice. Although N-cadherin is expressed at the time of gastrulation and neurulation, both neurulation and somitogenesis initiate apparently normally in homozygous mutant embryos. However, the resulting structures are often malformed. The somites of the mutant embryos are small, irregularly shaped, and less cohesive compared with those of their wild-type littermates, and the epithelial organization of the somites is partially disrupted. Undulation of the neural tube is also observed in the mutant embryos. Homozygous mutant embryos die by Day 10 of gestation. The mesodermal and endodermal cell layers of the yolk sac are separated in the mutants. The most dramatic cell adhesion defect is observed in the primitive heart; although myocardial tissue forms initially, the myocytes subsequently dissociate and the heart tube fails to develop normally. In vitro studies of cardiac myocytes derived from N-cadherin mutant embryos show that the cells can loosely aggregate and beat synchronously, demonstrating that electrical coupling can occur between N-cadherin-deficient cardiac myocytes. These results show that N-cadherin plays a critical role in early heart development as well as in other morphogenetic processes.
为了研究N-钙黏蛋白在体内的功能，我们在小鼠中对编码这种黏附蛋白的基因进行了突变。尽管N-钙黏蛋白在原肠胚形成和神经胚形成时表达，但在纯合突变胚胎中，神经胚形成和体节发生显然均正常起始。然而，最终形成的结构常常畸形。与野生型同窝仔相比，突变胚胎的体节小、形状不规则且黏附性较差，并且体节的上皮组织部分遭到破坏。在突变胚胎中还观察到神经管的波动。纯合突变胚胎在妊娠第10天死亡。卵黄囊的中胚层和内胚层细胞层在突变体中分离。在原始心脏中观察到最显著的细胞黏附缺陷；尽管心肌组织最初形成，但心肌细胞随后解离，心脏管无法正常发育。对源自N-钙黏蛋白突变胚胎的心肌细胞进行的体外研究表明，这些细胞可以松散聚集并同步跳动，这表明在缺乏N-钙黏蛋白的心肌细胞之间可以发生电偶联。这些结果表明，N-钙黏蛋白在早期心脏发育以及其他形态发生过程中起关键作用。
