Keränen S V, Kettunen P, Aberg T, Thesleff I, Jernvall J
Developmental Biology Program, Institute of Biotechnology, Biocenter 1, University of Helsinki, P.O. Box 56, Helsinki, FIN-00014, Finland.
Dev Genes Evol. 1999 Aug;209(8):495-506. doi: 10.1007/s004270050282.
Rodents have a toothless diastema region between the incisor and molar teeth which may contain rudimentary tooth germs. We found in upper diastema region of the mouse (Mus musculus) three small tooth germs which developed into early bud stage before their apoptotic removal, while the sibling vole (Microtus rossiaemeridionalis) had only a single but larger tooth germ in this region, and this developed into late bud stage before regressing apoptotically. To analyze the genetic mechanisms of the developmental arrest of the rudimentary tooth germs we compared the expression patterns of several developmental regulatory genes (Bmp2, Bmp4, Fgf4, Fgf8, Lef1, Msx1, Msx2, p21, Pitx2, Pax9 and Shh) between molars and diastema buds of mice and voles. In diastema tooth buds the expression of all the genes differed from that of molars. The gene expression patterns suggest that the odontogenic program consists of partially independent signaling cascades which define the exact location of the tooth germ, initiate epithelial budding, and transfer the odontogenic potential from the epithelium to the underlying mesenchyma. Although the diastema regions of the two species differed, in both species the earliest difference that we found was weaker expression of mesenchymal Pax9 in the diastema region than in molar and incisor regions at the dental lamina stage. However, based on earlier tissue recombination experiments it is conceivable that the developmental arrest is determined by the early oral epithelium.
啮齿动物在门齿和臼齿之间有一个无牙的齿间隙区域，该区域可能含有未发育完全的牙胚。我们在小鼠（小家鼠）的上颌齿间隙区域发现了三个小牙胚，它们在凋亡清除之前发育到早期芽阶段，而同胞田鼠（南欧田鼠）在该区域只有一个但更大的牙胚，并且这个牙胚在凋亡退化之前发育到晚期芽阶段。为了分析未发育完全的牙胚发育停滞的遗传机制，我们比较了小鼠和田鼠臼齿和齿间隙芽中几种发育调控基因（Bmp2、Bmp4、Fgf4、Fgf8、Lef1、Msx1、Msx2、p21、Pitx2、Pax9和Shh）的表达模式。在齿间隙牙胚中，所有基因的表达都与臼齿不同。基因表达模式表明，牙发生程序由部分独立信号级联组成，这些信号级联确定牙胚的确切位置、启动上皮出芽，并将牙发生潜能从上皮传递到下方的间充质。尽管两个物种的齿间隙区域不同，但在两个物种中我们发现的最早差异都是在牙板阶段齿间隙区域间充质Pax⁹的表达比臼齿和门齿区域弱。然而，根据早期的组织重组实验，可以想象发育停滞是由早期口腔上皮决定的。
