细胞命运决定和增殖贯穿了牙胚发育的整个过程，BMP和Wnt信号分子参与了牙胚发育，Noggin被公认为是BMP信号通路的特异性拮抗剂。本课题组前期研究提示：在早期牙上皮内过表达Noggin，除抑制BMP/MAPK外，还可能抑制Wnt/β-catenin；Wnt/β-catenin可能决定牙上皮命运，并可能协同BMP/MAPK调控上皮增殖。基于前期研究基础，本课题拟使用多种转基因小鼠模型和分子生物学手段解决以下关键科学问题：⑴ 在体外和体内研究Noggin是否可以抑制Wnt/β-catenin信号通路，并阐述其分子机制；⑵ 在牙胚发育早期牙上皮命运是否由Wnt/β-catenin信号决定并维持，而不受BMP/MAPK信号影响；⑶ 在牙胚发育早期上皮增殖是否由BMP/MAPK和Wnt/β-catenin协同影响；⑷ 在牙胚发育早期上皮内BMP/MAPK和Wnt/β-catenin是否互相调控。

The determination of dental epithelial fate and cell proliferation is very critical for early tooth development. Multiple BMP and Wnt signaling molecules are expressed and play important roles in early dental epithelium. Noggin is well recognized as an antagonist of BMP signaling pathway. However, our preliminary study suggests that overexpressed Noggin in the dental epithelium might inhibit Wnt/β-catenin signaling pathway besides BMP/MAPK pathway. In addition, Wnt/β-catenin pathway might be involved in determination of the dental epithelial fate, and synergistically control dental epithelial cell proliferation with BMP/MAPK pathway. Based on our preliminary data, the following scientific questions will be answered using a variety of transgenic mouse lines and molecular biological methods: (1) Whether Noggin is able to antagonize Wnt/β-catenin pathway in vitro and in vivo, and its underlying molecular mechanisms; (2) Whether the dental epithelial fate in early development is determined and maintained by Wnt/β-catenin pathway but not BMP/MAPK pathway; (3) Whether the cell proliferation rate of dental epithelium during early development is synergistically affected by BMP/MAPK and Wnt/β-catenin pathways; (4) Whether BMP/MAPK and Wnt/β-catenin pathways interact reciprocally in the early dental epithelium.