Fraser Gareth J, Berkovitz Barry K, Graham Anthony, Smith Moya M
MRC Centre for Developmental Neurobiology, King's College London, London, UK.
Evol Dev. 2006 Sep-Oct;8(5):446-57. doi: 10.1111/j.1525-142X.2006.00118.x.
Repeated tooth initiation occurs often in nonmammalian vertebrates (polyphyodontism), recurrently linked with tooth shedding and in a definite order of succession. Regulation of this process has not been genetically defined and it is unclear if the mechanisms for constant generation of replacement teeth (secondary dentition) are similar to those used to generate the primary dentition. We have therefore examined the expression pattern of a sub-set of genes, implicated in tooth initiation in mouse, in relation to replacement tooth production in an osteichthyan fish (Oncorhynchus mykiss). Two epithelial genes pitx2, shh and one mesenchymal bmp4 were analyzed at selected stages of development for O. mykiss. pitx2 expression is upregulated in the basal outer dental epithelium (ODE) of the predecessor tooth and before cell enlargement, on the postero-lingual side only. This coincides with the site for replacement tooth production identifying a region responsible for further tooth generation. This corresponds with the expression of pitx2 at focal spots in the basal oral epithelium during initial (first generation) tooth formation but is now sub-epithelial in position and associated with the dental epithelium of each predecessor tooth. Co-incidental expression of bmp4 and aggregation of the mesenchymal cells identifies the epithelial-mesenchymal interactions and marks initiation of the dental papilla. These together suggest a role in tooth site regulation by pitx2 together with bmp4. Conversely, the expression of shh is confined to the inner dental epithelium during the initiation of the first teeth and is lacking from the ODE in the predecessor teeth, at sites identified as those for replacement tooth initiation. Importantly, these genes expressed during replacement tooth initiation can be used as markers for the sites of "set-aside cells," the committed odontogenic cells both epithelial and mesenchymal, which together can give rise to further generations of teeth. This information may show how initial pattern formation is translated into secondary tooth replacement patterns, as a general mechanism for patterning the vertebrate dentition. Replacement of the marginal sets of teeth serves as a basis for discussion of the evolutionary significance, as these dentate bones (dentary, premaxilla, maxilla) form the restricted arcades of oral teeth in many crown-group gnathostomes, including members of the tetrapod stem group.
重复的牙齿起始现象在非哺乳类脊椎动物中经常发生（多牙列），它与牙齿脱落反复相关，且具有明确的连续顺序。这一过程的调控尚未在基因层面得到明确界定，用于持续生成替换牙（恒牙列）的机制是否与用于生成乳牙列的机制相似也尚不清楚。因此，我们研究了一组与小鼠牙齿起始相关的基因在硬骨鱼类（虹鳟鱼）替换牙生成过程中的表达模式。在虹鳟鱼发育的特定阶段，对两个上皮基因pitx2、shh和一个间充质基因bmp4进行了分析。pitx2的表达在前驱牙的基底外侧牙上皮（ODE）中上调，且在细胞增大之前，仅在舌后侧上调。这与替换牙生成的部位相吻合，确定了一个负责进一步牙齿生成的区域。这与pitx2在初始（第一代）牙齿形成过程中在基底口腔上皮中的焦点部位的表达相对应，但现在其位置在皮下，且与每个前驱牙的牙上皮相关。bmp4的共表达和间充质细胞的聚集确定了上皮-间充质相互作用，并标志着牙乳头的起始。这些共同表明pitx2和bmp4在牙齿部位调控中发挥作用。相反，shh的表达在第一批牙齿起始时局限于内侧牙上皮，在前驱牙的ODE中缺乏，而这些部位被确定为替换牙起始的部位。重要的是，在替换牙起始过程中表达的这些基因可作为“预留细胞”部位的标记，这些细胞是已确定的上皮和间充质牙源性细胞，它们共同可产生更多代牙齿。这些信息可能揭示了初始模式形成如何转化为次生牙替换模式，作为一种构建脊椎动物牙列模式的普遍机制。边缘牙齿组的替换作为讨论进化意义的基础，因为这些齿骨（齿骨、前颌骨、上颌骨）在许多冠群有颌类动物中形成了口腔牙齿的受限牙弓，包括四足动物干群的成员。
