Beta‐catenin is essential for ameloblast movement during enamel development

Beta‐catenin is a multifunctional protein that plays key roles in cadherin‐based cell adherens junctions and in the Wnt signaling pathway. The canonical Wnt/ β ‐catenin pathway can regulate transcription factors that control cell movement/invasion. We investigated whether β ‐catenin regulates ameloblast movement through canonical Wnt signaling. The morphological and physical properties of enamel were assessed in enamel from control and β ‐catenin conditional knockout ( cKO ) mice. Ameloblast‐lineage cells ( ALC ) were used to investigate the potential roles of β ‐catenin in cell migration and in E‐cadherin expression. Compared with controls, incisors from β ‐catenin cKO mice were short, blunt, and where enamel was present, it was soft and malformed. Scanning electron microscopy revealed a dysplastic rod pattern within the enamel of incisors from β ‐catenin cKO mice, and Vickers microhardness measurements confirmed that mice with β ‐catenin ablated from their enamel organ had enamel that was significantly softer than normal. Amelogenesis was disrupted in the absence of β ‐catenin and the ameloblasts did not differentiate properly. We further demonstrated that migration of ALC s was inhibited in vitro and that E‐cadherin expression was significantly up‐regulated when ALC s were treated with the β ‐catenin inhibitor, ICG ‐001. Beta‐catenin ablation causes enamel malformation in mice and this phenotype may occur, in part, by a lack of ameloblast differentiation and/or movement necessary to form the decussating enamel rod structure.