Keränen S V, Aberg T, Kettunen P, Thesleff I, Jernvall J
Developmental Biology Program, Institute of Biotechnology, Viikki Biocentre, P.O. Box 56, University of Helsinki, FIN-00014, Finland.
Dev Genes Evol. 1998 Nov;208(9):477-86. doi: 10.1007/s004270050206.
While the evolutionary history of mammalian tooth shapes is well documented in the fossil record, the developmental basis of their tooth shape evolution is unknown. We investigated the expression patterns of eight developmental regulatory genes in two species of rodents with different molar morphologies (mouse, Mus musculus and sibling vole, Microtus rossiaemeridionalis). The genes Bmp-2, Bmp-4, Fgf-4 and Shh encode signal molecules, Lef-1, Msx-1 and Msx-2, are transcription factors and p21CIP1/WAF1 participates in the regulation of cell cycle. These genes are all known to be associated with developmental regulation in mouse molars. In this paper we show that the antisense mRNA probes made from mouse cDNA cross-hybridized with vole tissue. The comparisons of gene expression patterns and morphologies suggest that similar molecular cascades are used in the early budding of tooth germs, in the initiation of tooth crown base formation, and in the initiation of each cusp's development. Furthermore, the co-localization of several genes indicate that epithelial signalling centres function at the three stages of morphogenesis. The earliest signalling centre in the early budding epithelium has not been reported before, but the latter signalling centres, the primary and the secondary enamel knots, have been studied in mouse. The appearance of species-specific tooth shapes was manifested by the regulatory molecules expressed in the secondary enamel knots at the areas of future cusp tips, whilst the mesenchymal gene expression patterns had a buccal bias without similar species-specific associations.
虽然哺乳动物牙齿形状的进化史在化石记录中有详细记载，但其牙齿形状进化的发育基础尚不清楚。我们研究了八种发育调控基因在两种具有不同臼齿形态的啮齿动物（小鼠，小家鼠和同胞田鼠，南欧田鼠）中的表达模式。基因Bmp - 2、Bmp - 4、Fgf - 4和Shh编码信号分子，Lef - 1、Msx - 1和Msx - 2是转录因子，p21CIP1/WAF1参与细胞周期调控。这些基因都已知与小鼠臼齿的发育调控有关。在本文中我们表明，由小鼠cDNA制备的反义mRNA探针与田鼠组织发生交叉杂交。基因表达模式和形态的比较表明，在牙胚的早期萌芽、牙冠基部形成的起始以及每个牙尖发育的起始过程中，使用了相似的分子级联反应。此外，几个基因的共定位表明上皮信号中心在形态发生的三个阶段发挥作用。早期萌芽上皮中最早的信号中心以前尚未见报道，但后两个信号中心，即初级和次级釉结，已在小鼠中进行过研究。物种特异性牙齿形状的出现表现为在未来牙尖区域的次级釉结中表达的调控分子，而间充质基因表达模式具有颊侧偏向性，没有类似的物种特异性关联。
