在出生缺陷中，心脏发育异常引起的先天性心脏病居于首位。心内膜内皮间质转化（EndMT）是心脏发育的重要环节，其异常与房室通道、流出道畸形发生相关。胚胎发育重要转录因子SOX7在心脏发育中的作用机制尚未阐明。本课题组前期研究发现SOX7表达于人胚心脏房室通道、流出道的心内膜及间质细胞。在3例流出道异常患儿中，SOX7基因存在突变，而且突变蛋白对潜在靶基因VE-cadherin、β-catenin的调控作用发生改变，提示SOX7可能通过VE-cadherin、β-catenin介导心内膜EndMT，影响心脏发育。为阐明该机制，本课题拟利用SOX7敲除小鼠、房室管/流出道移植物、细胞功能分析等技术手段，研究SOX7介导心内膜EndMT的机制，并筛查先心病中SOX7突变，分析突变体蛋白功能及其在先心病发生中的作用。本项目将拓宽对心脏发育和先心病致病机制的认识，为先心病的早期诊断、遗传咨询提供基础。

Congenital heart defects (CHD) due to abnormal heart development ranks top in birth defects. As a key part of heart development, aberrations of endocardial endothelial-to-mesenchymal transition (EndMT) is related to atrioventricular canal (AVC) and out flow tract (OFT) malformation. The role of the important embryonic development-related transcription factor, SOX7, during heart development, has not been revealed. Preliminary research of our group showed SOX7 is expressed in a subset of endothelial cells as well as mesenchymal cells of the AVC and OFT in the embryonic human heart, and mutations of SOX7 was found in 3 cases of patients with OFT malformation, wherein SOX7 mutants influenced candidate gene targets VE-cadherin and β-catenin, suggesting SOX7 can affect heart development via regulating endocardial EndMT with VE-cadherin and β-catenin. This research aims to elucidate the underlying mechanisms of SOX7-mediated endocardial EndMT by using SOX7-knockout mice experiments, AVC/OFT explant assays and analysis of cell functions. We’ll also screen for SOX7 mutations in CHD and analyze the functions of SOX7 mutants and their roles in CHD. This research will deepen our understandings of the mechanisms of the development of the heart and CHD, and provide the basis for early diagnosis and genetic counseling of CHD.