FGF signaling is necessary for the specification of the odontogenic mesenchyme

Tooth development is initiated by signals from the oral ectoderm which induce gene expression required for tooth development in the underlying mesenchyme. In this study, we have used Su5402, an inhibitor of FGF receptor signaling, to analyze the requirement of FGF signaling during early tooth development. We show that FGF signaling is necessary for expression of Pax9, a transcription factor required for development of all teeth, in prospective incisor and molar mesenchyme until E11.0. Expression of the LIM homeobox gene Lhx7 also requires FGF signaling until E11.0 whereas expression of its homologue Lhx6 and the homeobox transcription factor Barx1 already becomes independent of FGF signaling at E10.75. In contrast, ectodermal expression of several genes thought to be important for tooth development was unaffected by the block of FGF signaling. Finally, we show that expression of the TGFbeta antagonist Dan in prospective tooth mesenchyme requires ectodermal signals and can be induced by FGF-soaked beads but is maintained in mandibular explants in the absence of FGF signaling. Together, these results demonstrate that FGF signaling is required for development of both molar and incisor teeth and suggest that specification of tooth mesenchyme involves at least two FGF-dependent steps.