Transgenically ectopic expression of Bmp4 to the Msx1 mutant dental mesenchyme restores downstream gene expression but represses Shh and Bmp2 in the enamel knot of wild type tooth germ

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 i n which tooth development is arrested at the bud stage in an effort of resc uing Msx1 mutant tooth phenotype in vivo. Ectopic expression of a Bmp4 tran sgene driven by the mouse Msx1promoter in the dental mesenchyme restored th e 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 coul d be partially rescued to progress to the cap stage. The Msx1-Bmp4 transgen e was also able to rescue the alveolar processes and the neonatal lethality of the Msx1 mutants. In contrast, overexpression of Bmp4 in thee 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 alveol ar process formation. Expression of Shh and Bmp2 in the enamel knot may not represent critical signals for tooth patterning. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.