The Role of Wnt Signaling in Early Tooth Development

Objectives: Canonical Wnt signaling is evident throughout early mammalian tooth development, suggesting that it plays an important role during odontogenesis. However, the specific role of canonical Wnt signaling in initiation of tooth development remains unclear. Building up on our finding of a dental epithelial progenitor population that transiently expresses Fgf8 at the initiation stage and gives rise to the future dental lamina, we will investigate the role of Wnt signaling in early stages of tooth development.
Methods: Wnt signaling pathway was conditionally hyperactivated or inactivated in dental epithelium by respectively stabilizing or ablating the Wnt signal transducer β-catenin in dental epithelial progenitor cells at the initiation stage of odontogenesis. The resulting phenotype was evaluated using in-situ hybridization, whole-mount 3D imaging, and histology.
Results: Hyperactivating Wnt signaling pathway led to evagination of the dental epithelium into the oral cavity, as opposed to the normally occurring invagination into the underlying mesenchyme. In addition, upregulated Wnt signaling induced ectopic expression of odontogenic markers, including members of SHH, FGF, Wnt and BMP pathways. Conversely, tooth development was blocked at the initiation stage upon ablating Wnt signaling in dental epithelium. Interestingly, the expression of Shh and Wnt10b was lost as early as in the initiation stage upon abrogation of Wnt signaling, highlighting the dynamic interaction between these pathways.
Conclusions: These findings indicate that canonical Wnt signaling regulates dental epithelial growth and invagination, perhaps by modulation of other signaling pathways.