先天性心脏病（CHD）在我国位居出生缺陷首位，是影响儿童健康及人口生存质量的重大公共卫生问题。Dicer是调控miRNA成熟的关键酶，其缺失导致心衰，但在CHD发生中的作用机制尚不明确。我们预实验发现敲除Dicer的斑马鱼心包水肿，这与前期研究中cul4a缺失导致心脏发育异常的表型极为相似。进一步发现，Dicer影响Cul4a与Hippo关键酶Lats1及自噬相关蛋白Wipi2的结合。已知Dicer能引起Sirt7核质转移，故我们提出假说：Dicer缺失通过Sirt7介导Crl4a活性降低，Lats1累积使细胞自噬过度激活，最终导致心脏发育异常。为验证该假说，我们拟用Dicer敲除的细胞及动物模型，采用WISH、质谱分析等方法，明确Sirt7-Crl4a-Hippo信号轴对细胞自噬的调控，探讨Dicer在心脏发育及CHD发生中的作用机制，为CHD的遗传筛查及干预治疗提供理论依据及新的靶点。

Among the birth defects, Congenital Heart Disease (CHD) ranks the first place in China which is a major public health problem affecting the health of children and the quality of the population. Deletion of Dicer, a key enzyme that regulates maturation of miRNA, displayed heart failure. While, the impact of Dicer deficiency in the development of CHD is poorly understood. In our preliminary works, dicer knockdown embryos displayed pericardial edema defects that is similar to the cul4a morphants in our previous research. In addition, Dicer also affected the protein interactions between Cul4a, Lats1 and Wipi2. It is known that Dicer could cause the transfer of Sirt7 between nuclear and cytoplasm. Therefore, we hypothesized that dicer deficiency leads to decreased activity of Crl4a mediated by Sirt7, and the accumulation of Lats1 leads to over-activation of autophagy, which eventually leads to abnormal cardiac development. To test this hypothesis, we intend to utilize H9C2 in vitro and Dicer knockout mice and zebrafish models in vivo, and explore the function of Dicer in regulating the development of heart development by WIHC, mass spectroscopy and so on. Uncover the epigenetic mechanisms of Sirt7-Crl4a-Hippo signal axis in regulating cell autophagy and heart development, which could provide the basis and new targets for early diagnosis and genetic counseling of CHD.