Zhu Diqi, Fang Yabo, Gao Kun, Shen Jie, Zhong Tao P, Li Fen
Department of Pediatric Cardiology, Shanghai Children's Medical Center Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200127, China.
State Key Laboratory of Genetic Engineering, Zhongshan Hospital, School of Life Sciences, Fudan University, Shanghai 200438, China.
Int J Mol Sci. 2017 Feb 21;18(2):444. doi: 10.3390/ijms18020444.
Vascular endothelial growth factor A (Vegfa) signaling regulates cardiovascular development. However, the cellular mechanisms of Vegfa signaling in early cardiogenesis remain poorly understood. The present study aimed to understand the differential functions and mechanisms of Vegfa signaling in cardiac development. A loss-of-function approach was utilized to study the effect of Vegfa signaling in cardiogenesis. Both morphants and mutants for display defects in cardiac looping and chamber formation, especially the ventricle. Vegfa regulates the heart morphogenesis in a dose-dependent manner. Furthermore, the initial fusion of the bilateral myocardium population is delayed rather than endocardium. The results demonstrate that Vegfa signaling plays a direct impact on myocardium fusion, indicating that it is the initial cause of the heart defects. The heart morphogenesis is regulated by Vegfa in a dose-dependent manner, and later endocardium defects may be secondary to impaired myocardium-endocardium crosstalk.
血管内皮生长因子A（Vegfa）信号传导调节心血管发育。然而，Vegfa信号传导在早期心脏发生中的细胞机制仍知之甚少。本研究旨在了解Vegfa信号传导在心脏发育中的不同功能和机制。采用功能丧失方法研究Vegfa信号传导在心脏发生中的作用。Vegfa的形态突变体和基因突变体在心脏环化和腔室形成方面均表现出缺陷，尤其是心室。Vegfa以剂量依赖方式调节心脏形态发生。此外，双侧心肌群体的初始融合延迟，而非心内膜。结果表明，Vegfa信号传导对心肌融合有直接影响，表明它是心脏缺陷的初始原因。心脏形态发生受Vegfa以剂量依赖方式调节，后期的心内膜缺陷可能继发于心内膜-心肌相互作用受损。
