Spatiotemporal Expression Patterns of Critical Genes Involved in FGF Signaling during Morphogenesis and Odontogenesis of Deciduous Molar in Miniature Pig

Abstract Background The fibroblast growth factor (FGF) pathway plays important role in epithelial-mesenchymal interactions during tooth development. However, how the ligands, receptors, and inhibitors of the FGF pathway get involved into the epithelial-mesenchymal interactions are largely unknown in miniature pigs, which can be used as large animal models for similar tooth anatomy and replacement patterns to humans. Results In this study, we investigated the spatiotemporal expression patterns of critical genes encoding FGF ligands, receptors, and inhibitors in the third deciduous molar of the miniature pig at the cap, early bell, and late bell stages. With the methods of fluorescence in situ hybridization and real time RT-PCR, it was revealed that the expression of Fgf3, Fgf4, Fgf7, and Fgf9 mRNAs were located mainly in the dental epithelium and underlying mesenchyme at the cap stage. The expression levels of Fgf3 and Fgf7 in the mesenchyme were upregulated in the early bell stage and then concentrated in the odontoblasts layer in the late bell stage. In contrast, the expression levels of Fgf4 and Fgf9 in the mesenchyme were downregulated from the cap to bell stage. Gene expression analysis also suggested that Fgfr1 and Fgfr3 were the major receptors regulating dental calcification. Furthermore, the inhibitor-coding genes Sprouty 2 and Sprouty 4 were expressed in the epithelium and mesenchyme in the three stages, indicating that elaborate regulation occurred during dental morphogenesis. Conclusions The spatiotemporal expression pattern of FGF signaling provides the foundation for future studies aiming to fine-tune dental morphogenesis and odontogenesis by controlling the interactions between the dental epithelium and mesenchyme, thereby promoting tooth regeneration in large mammals.