BMP Signals Promote Proepicardial Protrusion Necessary for Recruitment of Coronary Vessel and Epicardial Progenitors to the Heart
BMP Signals Promote Proepicardial Protrusion Necessary for Recruitment of Coronary Vessel and Epicardial Progenitors to the Heart
复制标题
DOI：
10.1016/j.devcel.2010.07.017
复制
发表时间：
2010-08-17
影响因子：
11.8
通讯作者：
Mikawa, Takashi
中科院分区：
文献类型：
--
作者：
Ishii, Yasuo;Garriock, Robert J.;Mikawa, Takashi
冠状血管和心外膜起源于心外膜，称为心外膜原体。心外膜与心脏融合失败会导致严重的冠状动脉和心脏缺陷。然而，尚不清楚心外膜如何突出并附着在环形心管上。在这里，我们发现胚胎心肌中 BMP 配体的异位表达可以导致心外膜细胞靶向心脏的异常区域。此外，BMP 拮抗剂 Noggin 的错误表达会抑制心外膜前突以及与心脏的接触。最后，心外膜外植体优先向共培养的心脏部分扩展。这种偏好可以被 BMP2/4 模仿并被 Noggin 抑制。这些结果支持了一种模型，其中心肌衍生的 BMP 信号通过指导冠状动脉祖细胞的形态发生运动来调节冠状动脉祖细胞进入心脏的特定部位。
The coronary vessels and epicardium arise from an extracardiac rudiment called the proepicardium. Failed fusion of the proepicardium to the heart results in severe coronary and heart defects. However, it is unknown how the proepicardium protrudes toward and attaches to the looping heart tube. Here, we show that ectopic expression of BMP ligands in the embryonic myocardium can cause proepicardial cells to target aberrant regions of the heart. Additionally, misexpression of a BMP antagonist, Noggin, suppresses proepicardium protrusion and contact with the heart. Finally, proepicardium explant preferentially expands toward a cocultured heart segment. This preference can be mimicked by BMP2/4 and suppressed by Noggin. These results support a model in which myocardium-derived BMP signals regulate the entry of coronary progenitors to the specific site of the heart by directing their morphogenetic movement.