先天性心脏病（先心病）居出生缺陷首位，其发病机制探索对先心病一级预防有重要意义。心脏胚胎发育过程中众多基因的顺序精确转录调控是胚胎正常发育的必要前提，而组蛋白乙酰化修饰是调控基因转录的重要途径。心脏胚胎发育中，心肌细胞定向迁移在房室间隔闭合与流出道形成中作用至关重要，组蛋白乙酰化修饰同样精确调控平面细胞极性（PCP）途径作用下的心肌细胞迁移。课题组前期应用药物干扰组蛋白乙酰化/去乙酰化修饰的动态平衡，成功建立了先心病动物模型，但其机制尚需深入探索。本项目利用表观遗传学的研究工具，对组蛋白乙酰化修饰失衡对PCP途径相关基因（HDACs、Vangl2及Scrib）表达调控的影响，以及新生小鼠心肌细胞迁移运动轨迹、骨架蛋白极性分布变化等进行研究，力图在调控基因表达层面，从心肌细胞迁移的全新角度揭示先心病的重要发病机制，为先心病的病因预防工作及环境致畸的病因学研究提供一条崭新的思路。

Congenital heart disease (CHD) ranks the first in the birth defects. For this reason, applying epigenetic theory to study the mechanisms of clinical disease at the gene expression level might have great significance in scientific theory of primary prevention of congenital heart disease. Heart development involves the order of expression of numerous genes during embryonic development. Normal development of embryon depended on the finely tuned regulation of gene transcription and acetylation of histone plays an important role in this process. During the embryonic cardiac development, myocardial cell directional migration plays a vital role in atrioventricular septal closure and outflow tract formation, and histone acetylation modification also precisely regulates myocardial cell migration under the action of planar cell polarity (PCP) pathway. Our preliminary application chose mice to study the influence of histone acetylation imbalance in the PCP pathway to the expression and regulation of related genes and the expression and regulation, interfered with histone acetylation / deacetylation modified dynamic balance, successfully established animal model of congenital heart disease, but its mechanism still need further exploration. By means of epigenetics research tools, this project focus related genes ( HDACs, Vangl2 and Scrib ) expression regulation of histone acetylation modification imbalance in the PCP pathway, as well as myocardial cell migration movement and polar distribution of cytoskeletal proteins in newborn mouse, trying to reveal the important pathogenesis of CHD, and than makes some exploration to study the underlying cause of CHD with a new perspective, which may not only lay a solid experimental and theoretical basis for the prevention of CHD but also provide a new opinion on etiology research of the environmental factors lead to the etiology of congenital malformations.