Trinh L A, Stainier Didier Y R
Department of Biochemistry and Biophysics, Programs in Developmental Biology, Genetics and Human Genetics, University of California, San Francisco, San Francisco, CA 94143, USA.
Dev Cell. 2004 Mar;6(3):371-82. doi: 10.1016/s1534-5807(04)00063-2.
Several genes have been implicated in heart tube formation, yet we know little about underlying cellular mechanisms. We analyzed the cellular architecture of the migrating myocardial precursors, and find that they form coherent epithelia that mature as they move medially. Mutant analyses indicate that the cardia bifida locus natter (nat) is required for the integrity of the myocardial epithelia. We positionally cloned nat and show that it encodes Fibronectin. During myocardial migration, Fibronectin is deposited at the midline between the endoderm and endocardial precursors, and laterally around the myocardial precursors. Further analyses show that Fibronectin deposition at the midline is required for the timely migration of myocardial precursors, but dispensable for the migration process itself. In the complete absence of Fibronectin, adherens junctions between myocardial precursors do not form properly, suggesting that cell-substratum interactions are required for epithelial organization. These data suggest that myocardial migration is dependent on epithelial integrity.
已有多个基因被认为与心脏管形成有关，但我们对其潜在的细胞机制知之甚少。我们分析了迁移的心肌前体细胞结构，发现它们形成连贯的上皮细胞，并在向内侧移动时成熟。突变分析表明，心脏双裂位点natter（nat）是心肌上皮细胞完整性所必需的。我们通过定位克隆得到了nat，并表明它编码纤连蛋白。在心肌迁移过程中，纤连蛋白沉积在内胚层和心内膜前体细胞之间的中线处，以及心肌前体细胞周围的外侧。进一步分析表明，中线处的纤连蛋白沉积是心肌前体细胞及时迁移所必需的，但对迁移过程本身并非必不可少。在完全没有纤连蛋白的情况下，心肌前体细胞之间的黏着连接无法正常形成，这表明上皮组织的形成需要细胞与基质的相互作用。这些数据表明，心肌迁移依赖于上皮细胞的完整性。
