牙胚发育中Mint调控上皮-间充质相互作用机理的研究

项目名称： 牙胚发育中Mint调控上皮-间充质相互作用机理的研究

项目编号： No.81200757

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学二处

项目作者： 朱明慧

作者单位： 中国人民解放军第四军医大学

项目金额： 24万元

中文摘要： 牙胚发育中上皮-间充质相互作用的分子调控机理不明是严重制约牙再生的瓶颈之一。关键基因功能不明制约了牙胚分子调控机理的研究进展。Mint是新近发现的转录调控因子，是牙胚发育关键信号Notch负调控蛋白，可与牙胚关键转录因子Msx2、Cbfα1作用，调节矿化相关蛋白骨钙素的转录。前期研究发现：Mint基因敲除小鼠牙胚釉结、牙乳头不能正常形成，提示该基因是调控牙胚发育关键基因，但它在牙胚中的功能和对上皮-间充质相互作用的调控机理并不清楚。本项目利用Mint基因敲除小鼠，结合器官培养、组织培养技术研究Mint敲除后牙胚畸形变化和相关信号分子表达，确定其参与的信号通路；采用组织重组技术研究Mint调控成牙潜能在上皮和间充质间转移的分子机理；从而明确Mint是牙胚发育中调控上皮-间充质相互作用的关键调控因子，为牙齿发育分子网络调控体系提供新的理论基础，为牙再生中诱导牙齿发育重新启动的策略提供实验依据。

中文关键词： 牙胚发育；基因敲除；组织重组；信号通路；

英文摘要： During the tooth development, the molecular mechanism of epithelial-mesenchymal interactions is unknown. It is a serious bottleneck to restrict the tooth regeneration. The key gene function is unknown, which obstructs the research progress of molecular mechanisms during tooth development. Mint is a newly discovered transcription factor. Mint has been reported to act as a suppressor of Notch signaling, which plays an important role in tooth development. Mint enhances Cbfα1 activation of multiprotein complexes assembled by the OCFRE. Msx2 targets this complex as a mechanism of transcriptional inhibition. In osteoblasts, Mint may serve as a nuclear matrix platform that organizes and integrates osteogenic transcriptional responses. Previous data have shown that enamal knot and dental papilla fail to form in Mint-/- tooth germ. Although these results indicate that it is a key modulating gene, it is still unknown that the mechanism how Mint regulates reciprocal epithelial-mesenchymal interactions during the tooth development. In order to gain an insight into the molecular mechanism, We use Mint knockout mice embryos for organ culture and tissue culture to investage the changes in molecular expression and tooth germ. Then gene expression analysis using in situ hybridization will be combined with classical tissue recomb

英文关键词： tooth development；gene knock-out；signaling pathway；tissue recombination；