Weill Cornell Medical College, Department of Medicine, Division of Cardiology, New York, NY, USA.
Mech Dev. 2010 Sep-Dec;127(9-12):472-84. doi: 10.1016/j.mod.2010.08.005. Epub 2010 Aug 31.
Cardiac neural crest (CNC) plays a requisite role during cardiovascular development and defects in the formation of CNC-derived structures underlie several common forms of human congenital birth defects. Migration of the CNC cells to their destinations as well as expansion and maintenance of these cells are important for the normal development of the cardiac outflow tract and aortic arch arteries; however, molecular mechanisms regulating these processes are not well-understood. Fibronectin (FN) protein is present along neural crest migration paths and neural crest cells migrate when plated on FN in vitro; therefore, we tested the role of FN during the development of the CNC in vivo. Our analysis of the fate of the neural crest shows that CNC cells reach their destinations in the branchial arches and the cardiac outflow tract in the absence of FN or its cellular receptor integrin α5β1. However, we found that FN and integrin α5 modulate CNC proliferation and survival, and are required for the presence of normal numbers of CNC cells at their destinations.
心脏神经嵴（CNC）在心血管发育中起着必要的作用，而 CNC 衍生结构形成的缺陷是几种常见人类先天性出生缺陷的基础。CNC 细胞向其目的地的迁移以及这些细胞的扩增和维持对于心脏流出道和主动脉弓动脉的正常发育很重要；然而，调节这些过程的分子机制还不是很清楚。纤维连接蛋白（FN）蛋白存在于神经嵴迁移路径上，并且神经嵴细胞在体外铺板于 FN 上时会迁移；因此，我们测试了 FN 在体内 CNC 发育过程中的作用。我们对神经嵴命运的分析表明，在没有 FN 或其细胞受体整合素α5β1 的情况下，CNC 细胞到达鳃弓和心脏流出道的目的地。然而，我们发现 FN 和整合素α5 调节 CNC 的增殖和存活，并且对于 CNC 细胞在其目的地存在正常数量是必需的。
