Shanghai Pediatric Congenital Heart Disease Institute and Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China.
Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Sci Signal. 2018 Feb 27;11(519):eaah5770. doi: 10.1126/scisignal.aah5770.
During coronary vasculature development, endothelial cells enclose the embryonic heart to form the primitive coronary plexus. This structure is remodeled upon recruitment of epicardial cells that may undergo epithelial-mesenchymal transition (EMT) to enable migration and that give rise to smooth muscle cells. In mice expressing a loss-of-function mutant form of , a gene involved in ciliogenesis, the enclosure of the surface of the heart by the subepicardial coronary plexus was accelerated because of enhanced chemotactic responses to Shh. Coronary arteries, but not coronary veins in mutant mice, showed reduced smooth muscle cell coverage. In addition, mutant hearts had reduced expression of EMT and mesenchymal markers and had fewer epicardium-derived cells (EPDCs) that showed impaired migration. Epicardium-specific deletion of recapitulated the coronary artery defect of the mutant. Thus, Wdpcp promotes epithelial EMT and EPDC migration, processes that are required for remodeling of the coronary primitive plexus. The mutant mice will be a useful tool to dissect the molecular mechanisms that govern the remodeling of the primitive plexus during coronary development.
在冠状动脉血管发育过程中，内皮细胞包围胚胎心脏形成原始冠状丛。在招募心外膜细胞后，该结构会发生重塑，心外膜细胞可能经历上皮-间充质转化（EMT）以促进迁移，并产生平滑肌细胞。在表达一种参与纤毛发生的基因 的功能丧失突变体的小鼠中，由于对 Shh 的趋化反应增强，心外膜下冠状丛对心脏表面的包围加速。在 突变小鼠中，冠状动脉而非冠状静脉的平滑肌细胞覆盖率降低。此外， 突变心脏中 EMT 和间充质标志物的表达减少，心外膜衍生细胞（EPDC）数量减少，且迁移能力受损。心外膜特异性敲除 可重现 突变小鼠的冠状动脉缺陷。因此，Wdpcp 促进上皮 EMT 和 EPDC 迁移，这些过程是重塑原始冠状丛所必需的。 突变小鼠将是解析在冠状动脉发育过程中支配原始丛重塑的分子机制的有用工具。
