牙齿组织工程是未来解决牙齿缺失最为理想的手段。然而，牙发育机制尚不清楚成为制约瓶颈。课题组前期研究证实，p75NTR通过改变成牙关键因子Dlx/Msx的活性参与牙发育调控，进而预实验发现Mage-D1可能是p75NTR的下游桥梁信使。基于此，提出了参与牙发育调控的信号通路假说p75NTR—Mage-D1—Dlx/Msx。本项目拟通过相关实验检测手段，从分子和细胞水平明确Mage-D1与上游p75NTR、下游Dlx/Msx结合的功能区与关键位点，确证p75NTR—Mage-D1—Dlx/Msx信号转导轴的存在，阐明该通路的级联激活与信号传递机制；进而通过细胞体外诱导、在体成牙能力、Mage-D1敲除小鼠，观察p75NTR、Mage-D1和Dlx/Msx的表达规律与相关性，从细胞功能和基因遗传角度验证所提出的信号通路假说，探明其确切的调控作用，为揭示牙发育机制、推进牙齿组织工程提供新的思路。

Dental tissue engineering would be the best way to solve the problem of tooth loss in the future. However, the mechanism under tooth morphogenesis is even unclear, which becomes a bottleneck limiting the development of dental tissue engineering. In our previous research, p75NTR have been confirmed to play a crucial role in tooth development and mineralization, via changing the active factor of Dlx/Msx, the key factor of tooth development. Furthermore, Mage-D1 was found probably to be the important downstream bridge messenger of p75NTR in our preliminary data. Based on the evidence, the Mage-D1-mediated signaling pathway of p75NTR--Mage-D1--Dlx/Msx was firstly put forward by us. This project is firstly aim to define the functional regions and key sites of Mage-D1 binding to upstream p75NTR and downstream Dlx/Msx in both molecular and cellular levels through relevant experimental detection methods. Then to confirm the existence of p75NTR--Mage-D1--Dlx/Msx signal transduction axis and to reveal the mechanism of cascade activation. Moreover, this project is to investigate the expression pattern and correlation of p75NTR, Mage-D1 and Dlx/Msx by in vitro or in vivo odontogenic induction and Mage-D1 knockout mice. The effects of the proposed signaling pathway hypothesis is furtherly confirmed from the cell function and gene heredity. This project would provide new ideas for revealing the molecular mechanism under tooth development and promoting the process of dental tissue engineering.