Zhao X, Zhang Z, Song Y, Zhang X, Zhang Y, Hu Y, Fromm S H, Chen Y
Department of Cell and Molecular Biology and Center for Bioenvironmental Research, Tulane University, New Orleans, LA 70118, USA.
Mech Dev. 2000 Dec;99(1-2):29-38. doi: 10.1016/s0925-4773(00)00467-6.
Bmp4 is a downstream gene of Msx1 in early mouse tooth development. In this study, we introduced the Msx1-Bmp4 transgenic allele to the Msx1 mutants in which tooth development is arrested at the bud stage in an effort of rescuing Msx1 mutant tooth phenotype in vivo. Ectopic expression of a Bmp4 transgene driven by the mouse Msx1promoter in the dental mesenchyme restored the expression of Lef-1 and Dlx2 but neither Fgf3 nor syndecan-1 in the Msx1 mutant molar tooth germ. The mutant phenotype of molar but not incisor could be partially rescued to progress to the cap stage. The Msx1-Bmp4 transgene was also able to rescue the alveolar processes and the neonatal lethality of the Msx1 mutants. In contrast, overexpression of Bmp4 in the wild type molar mesenchyme down-regulated Shh and Bmp2 expression in the enamel knot, the putative signaling center for tooth patterning, but did not produce a tooth phenotype. These results indicate that Bmp4 can bypass Msx1 function to partially rescue molar tooth development in vivo, and to support alveolar process formation. Expression of Shh and Bmp2 in the enamel knot may not represent critical signals for tooth patterning.
在小鼠早期牙齿发育过程中，Bmp4是Msx1的下游基因。在本研究中，我们将Msx1 - Bmp4转基因等位基因导入Msx1突变体中，这些突变体的牙齿发育在芽期停滞，目的是在体内挽救Msx1突变体的牙齿表型。由小鼠Msx1启动子驱动的Bmp4转基因在牙间充质中的异位表达恢复了Msx1突变体磨牙牙胚中Lef - 1和Dlx2的表达，但未恢复Fgf3和syndecan - 1的表达。磨牙而非切牙的突变表型可部分挽救至帽状期。Msx1 - Bmp4转基因还能够挽救Msx1突变体的牙槽突和新生致死性。相比之下，在野生型磨牙间充质中过表达Bmp4会下调牙釉质结（牙齿形态发生的假定信号中心）中Shh和Bmp2的表达，但未产生牙齿表型。这些结果表明，Bmp4可以绕过Msx1的功能，在体内部分挽救磨牙的牙齿发育，并支持牙槽突的形成。牙釉质结中Shh和Bmp2的表达可能不代表牙齿形态发生的关键信号。
