Molecular Genetics of Tooth Development

牙齿发育是一个高度调节的过程，由许多编码生长因子、转录因子和细胞外基质蛋白的基因协调。牙齿发育正常和异常的分子机制尚未得到很好的描述。我们已开始研究常见牙病的候选基因，如牙本质发育不全、牙本质发育不良和成骨不全，以及与牙齿矿化有关的生长因子基因。牙本质涎磷蛋白基因是DGI-II的首选候选基因。它编码一种非胶原蛋白，在牙齿发育过程中特异地在成牙本质细胞和成釉细胞中表达。我们克隆和鉴定了小鼠DSPP同源基因，并以其基因座小鼠胚胎干细胞为靶点，建立了DGI-II的基因敲除模型。其次，利用DSPP启动子，我们针对牙齿发育中的候选基因进行表达，以阐明它们在牙齿发育中的具体作用。目前正在进行牙本质发生、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。

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