Wnt信号调节蛋白Gpr177在小鼠上腭发育中的功能研究

项目名称： Wnt信号调节蛋白Gpr177在小鼠上腭发育中的功能研究

项目编号： No.31201090

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 发育生物学与生殖生物学

项目作者： 朱晓静

作者单位： 杭州师范大学

项目金额： 24万元

中文摘要： 腭裂是常见人类新生头面部缺陷，其成因涉及上腭发生过程中多种遗传及环境因素。上腭的发育是通过其上皮组织和相邻间充质之间复杂的信号网络调控的，其中就包括Wnt信号的作用。以前有关Wnt信号的研究主要集中在Wnt信号接受细胞中Wnt通路蛋白，对于Wnt产生细胞中其调节蛋白的研究还很少。Gpr177是果蝇Wnt转运调节蛋白Wntless在小鼠中的同源蛋白，在小鼠胚胎上腭发生过程中的上皮和间充质部位均有表达。初步研究发现敲除神经嵴细胞的Gpr177会导致腭裂，然而其分子机制还不清楚。另外，Gpr177在上腭上皮也有表达，这部分的Gpr177是否也参与调控上腭发育也有待研究。因此，本项目将利用Cre-LoxP系统分别在小鼠胚胎上皮组织以及间充质中敲除Gpr177功能，并结合研究Gpr177对Wnt信号的控制作用，分析Gpr177在小鼠上腭器官发育中的分子控制，力争为腭裂的研究提供重要线索。

中文关键词： Wntless/Gpr177；发育；腭裂；wnt；器官

英文摘要： Clefts of the palate are common human craniofacial birth defects, involving multiple genetic and environmental causes. They appear to be caused by multiple genetic and environmental factors during palatogenesis. The development of the secondary palate is coordinated by a complex network of signaling pathways between epithelium and mesenchyme, which involves Wnt signaling. Previous studies have concentrated on components of Wnt pathway in Wnt signal-receiving cells. However, little is known about the regulation of Wnt in signal-producing cells. Here, we describe that Gpr177, the mouse orthologue of Drosophila Wnt trafficking regulator Wntless, is expressed in both epithelium and mesenchyme during palatogenesis. Deletion of Gpr177 in neural crest cells leads to cleft palate. However, the molecular mechanism is unclear. Additionally, Gpr177 is also expressed in epithelium; whether epithelial Gpr177 participates in regulation of secondary palate development remains to be understood. In this project, we are to use Cre-LoxP system to separately delete mouse epithelial and mesenchymal Gpr177, combining with studying its function in Wnt regulation, to analyze mechanism of Gpr177 in molecular control of mouse palate organ development, and to provide important clues for research of cleft palate.

英文关键词： Wntless/Gpr177；development；cleft palate；wnt；organ