先天性心脏病发病率高，严重威胁患儿的生命与健康。极其复杂的心脏基因调控网络控制了心脏的正常发育过程以及心血管疾病的发生发展，多种心脏转录因子协同参与其间。人类VGLL4基因定位于染色体3p25.3这一先天性心脏病易感区段内，编码一个转录辅因子，并且与之发生相互作用的多个转录因子都与心脏发育密切相关。而目前国际上对VGLL4在心脏领域内的研究甚少，因此本课题将以斑马鱼为模型，利用CRISPY/Cas9技术“敲除”目的基因，过表达目的基因进行功能“挽救”等多项分子生物学和生物化学技术深入研究VGLL4这一转录辅因子如何精细调控胚胎心脏发育过程。心脏的发育过程极其复杂，轻微扰乱即可造成严重后果。大量转录相关因子与心脏发育密切相关，因此对心脏发育过程中基因表达调控的研究将有助于我们找到疾病根源以及药物靶点，并为改进遗传咨询和先天性心脏病干预提供指导。

Congenital heart disease（CHD）threaten seriously the life and health of children. Complicated gene regulatory networks (GRNs) control the normal cardiac development and cardiovascular diseases, a variety of cardiac transcription factors synergistically involved in GRNs. The human VGLL4 gene is located in a CHD susceptibility locus on chromosome 3p25.3, which encodes a transcription cofactor, moreover, multiple interaction transcription factors of VGLL4 are implicated in heart development. While the current research on VGLL4 in the heart is still rare, here we will use zebrafish as model organism, a variety of experimental methods such as CRISPR/Cas9-mediated gene knockout technology to study the fine-tuned role of VGLL4 in cardiac development. Transcription regulation is tightly associated with heart development, more research work in this field will help us to find the cause of CHD and the drug target, and to improve the genetic counseling and disease intervention.