Antagonistic signals between BMP4 and FGF8 define the expression of Pitx1 and Pitx2 in mouse tooth-forming anlage

Members of the Pitx/RIEG family of homeodomain-containing transcription fac tors have been implicated in vertebrate organogenesis. In this study, we ex amined the expression and regulation of Pitx1 and Pitx2 during mouse tooth development. Pitx1 expression is detected in early development in a widespr ead pattern, in both epithelium and mesenchyme, covering the tooth-forming region in the mandible, and is then maintained in the dental epithelium fro m the bud stage to the late bell stage. Pitx2 expression, on the other hand , is restricted to the dental epithelium throughout odontogenesis. Interest ingly, from E9.5 to E10.5, the expression domains of Pitx1 and Pitx2, in th e developing mandible, overlap with that of Fgf8 but are exclusive to the z one of Bmp4 expression. Bead implantation experiments demonstrate that ecto pic expression of Fgf8 can induce/maintain the expression of both Pitx1 and Pitx2 at E9.5. In contrast, Bmp4-expressing tissues and BMP4-soaked beads were able to repress Pitx1 expression in mandibular mesenchyme and Pitx2 ex pression in the presumptive dental epithelium, respectively. However, the e ffects of FGF8 and BMP4 are transient. It thus appears that the early expre ssion patterns of Pitx1 and Pitx2 in the developing mandible are regulated by the antagonistic effects of FGF8 and BMP4 such that the Pitx2 and Pitx2 expression patterns are defined. These results indicate that the epithelial -derived signaling molecules are responsible not only for restricting speci fic gene expression in the dental mesenchyme, but also for defining gene ex pression in the dental epithelium. (C) 2000 Academic Press.