先天性唇腭裂（CLP）是颌面部最常见的发育畸形，在我国发生率为1.82‰，造成患儿颌面畸形，严重影响患儿身心健康，对患者家庭和社会造成很大负担。其病因复杂，遗传因素和环境因素均有重要作用。自噬是机体对体内不利微环境的一种适应机制，其异常可导致发育异常。我们前期研究发现小型猪腭部发育中有自噬体出现，mRNA表达谱分析发现腭部发育各阶段均有自噬相关因子的差异表达；利用我们自己建立的成熟的Tgfbr1诱导性条件敲除小鼠腭裂模型研究发现敲除Tgfbr1后腭裂组织自噬相关蛋白表达异常，本课题将以此为基础，分别从遗传和环境因素着手，在组织和细胞学层面研究自噬对腭部发育的影响，及其与TGF-β信号通路以及低氧在小鼠腭部发育中的调控作用，并寻找其它相关基因，多角度的探讨自噬在腭部发育中的功能机制，寻找关键靶点，从而扩大对唇腭裂发病机制的了解，做好早期预防及诊断治疗，进而减少唇腭裂的发生。

The most frequent birth defects of craniofacial abnormalities are the congenital cleft lip/palate(CLP). In China, occurrence of CLP estimates 1.82%, which results in complications affecting speech, feeding, hearing, appearance and psychological development. Patients and their families will undergo multiple rounds of surgical repair starting in the first year of life and may continue until 18 or 20 years old. CLP is etiologically heterogeneous and this has critical implications for understanding the biology of facial development, how environmental risks interact with genetic factors and how we can incorporate known etiologic variables to improve clinical care. Autophagy is an evolutionarily conserved cellular process through which long-lived proteins and damaged organelles are recycled to maintain energy homeostasis and is more widely viewed as a basic cell survival mechanism to combat environmental stressors. Disturbance of autophagy may induce craniofacial malformations. Using histological and ultrastructural methods, we investigated the developmental stages of the palate in miniature pigs which was from E26-50 and found autophagosome or autophagosome like structures with variable autophagy associated genes expressions at different stages in palate development. Also we used a previously generating mutant animal model, in which tamoxifen inducible loss of Tgfbr1 in epithelium cells which is more accurately to lead to cleft palate and is differed from previous cleft palate in Tgfbr1 conditional knockout mice model and detected that autophagy associated genes expressions were different from the control in palate. Based on these, we will investigate the mechanism of genetic and environmental triggers on autophagy during mice palate development in vivo and in vitro, especially the crosstalk between autophagy and TGF-β signaling/hypoxia. The study of these genes and their molecular pathway will provide a useful and informative route with which to gain a better understanding of human CLP, and benefits of precise diagnosis, accurate risk assessment and genetic counseling can be achieved. And the potential for treatments and preventative therapies may also become a reality to reduce CLP.