Molecular Genetics of Tooth Development

牙齿的发育是一个高度调控的过程，由许多基因编码的生长因子，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还没有得到很好的表征。近年来，人们对牙本质发育不良（dentinogenesis diluta，DGI）、牙本质发育不良（dentin dysplasia）、成骨不全（osteognensis imperfcta）等常见牙病的候选基因以及与牙矿化有关的生长因子基因进行了研究，其中牙本质涎磷蛋白（Dentin sialophosphoprotein，DSPP）基因是DGI-Ⅱ的主要候选基因。它编码一种非胶原蛋白，在牙齿发育过程中在成牙本质细胞和成釉细胞中特异性表达。我们克隆并鉴定了鼠DSPP同源物，并靶向其位点小鼠胚胎干细胞，以产生DGI-II的基因敲除模型。其次，利用DSPP启动子，我们靶向候选基因在牙齿发育中的表达，以阐明其在牙齿发育中的特定作用。研究正在进行中，以表征牙本质发生、分子遗传学、基因敲除、生长因子、细胞外基质、矿化

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