腭裂是最常见的先天畸形之一，地塞米松等激素的摄入是导致腭裂发生的重要病因。已知地塞米松是凋亡的强诱导剂，但是凋亡在腭裂的发生过程中到底如何变化尚存在争议。 BMP-2能调节凋亡，并已被证实与腭裂的发生相关。而其上游基因GATA-6作为与胚胎发育密切相关的转录调节因子，能引起多个胚层来源的器官发育异常。本课题负责人前期在胚胎干细胞模型上的工作发现，胚胎形成期GATA-6敲除会导致BMP-2的表达受抑制，使凋亡增加。而在腭裂发生的过程中，GATA-6是否通过影响BMP-2的表达调节凋亡，进而引起腭裂，尚未见文献报道。 本课题拟通过建立地塞米松诱导腭裂的动物模型，并使用基因抑制技术下调腭间充质细胞内的GATA-6，借助分子生物学检测方法，分析腭裂与凋亡之间的关系，并确定该凋亡是否通过GATA-6和BMP-2进行调控，从胚胎发育角度探讨腭裂发生的分子机制，为今后先天性腭裂的预防和治疗提供新的思路

Cleft palate is one of the most common congenital malformation, the intake of dexamethasone as a kind of glucocorticoid is a important etiology of cleft palate. BMP-2 can regulate apoptosis, and has already been identified to contribute to the appearence of cleft palate.While its upstream gene, GATA-6, is a transcription factor that can induce dysplasia of organs derived from multiple germ-layers. The previous research of this project applicator on the model of embryonic stem cells suggested the knock out of GATA-6 may inhibit the expression of BMP-2 ,and induce apoptosis. However, during the pathogenesis of cleft palate , whether GATA-6 can regulate apoptosis through the influence of BMP-2 has not been reported yet. We plan to construct an animal model of cleft palate and knock down GATA-6 in the palatal mesenchymal cells,then analysis the relationship between cleft palate and apoptosis by molecular biological methods,make sure whether this apoptosis is mediated by GATA-6 and BMP-2, analyze their molecular mechanism in the aspect of embryonic development .This research may discover another molecular mechanism of pathogenesis of cleft palate, and provide a novel research idea for the prevention and treatment of congenital cleft palate.