Molecular Genetics of Tooth Development

牙齿发育是一个高度调控的过程，由许多基因编码生长因子、转录因子和细胞外基质蛋白。正常和异常牙齿发育的分子机制尚不清楚。我们已经开始了对牙本质发育不全（DGI）、牙本质发育不良、成骨发育不全等常见牙齿疾病的候选基因以及与牙齿矿化有关的生长因子基因的研究。牙本质唾液磷蛋白（DSPP）基因是DGI-II的主要候选基因。它编码一种非胶原蛋白，这种蛋白在牙齿发育过程中在成牙细胞和成釉细胞中特异性表达。我们克隆并鉴定了小鼠DSPP同源物，并将其定位于小鼠胚胎干细胞，以建立DGI-II基因敲除模型。其次，我们利用DSPP启动子靶向候选基因在牙齿发育中的表达，以描述它们在牙齿发育中的具体作用。牙本质发生、分子遗传学、基因敲除、生长因子、细胞外基质、矿化等方面的研究正在进行中

Tooth development is a highly reguated process orchestrated by a number of genes that encode growth factors, transcription factors and extracellular matrix proteins. Molecular mechanisms underlying the noral and abnormal tooth development is not well characterized. We have initiated studies that focus on the candidate genes for the common tooth disorders such as dentinogenesis imperfecta (DGI), dentin dysplasia and osteognensis imperfcta as well as growth factor genes involved in tooth mineralization.Dentin sialophosphoprotein (DSPP) gene is a prime candidate for DGI-II. It encodes a non-collagenous protein that is specifically expressed in odontoblasts and ameloblasts during tooth development. We have clonedand characterized the murine DSPP homolog and targeted its locus mouse embryonic stem cells in order to generate a gene knockout model for DGI-II. Secondly, using the DSPP promoter we targeted expression of candidate genes in developing tooth to delineate their specific roles in tooth development. Studies are underway to characterize the - Dentinogenesis, molecular genetics, gene knockout, growth factors, extracellular matrix, mineralization