title: Beta-catenin is essential for ameloblast movement during enamel development.
abstract: 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 ALCs was inhibited in vitro and that E-cadherin expression was significantly up-regulated when ALCs 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.
authors.affiliation: Department of Mineralized Tissue Biology and Harvard School of Dental Medicine, Forsyth Institute, Cambridge, MA, USA.
authors.forename: Xiaomu
authors.initials: X
authors.lastname: Guan
authors.affiliation: Departments of Dermatology and Cell & Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Mingang
authors.initials: M
authors.lastname: Xu
authors.affiliation: Departments of Dermatology and Cell & Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Millar
authors.affiliation: Division of Biosciences, College of Dentistry, Ohio State University, Columbus, OH, USA.
authors.forename: John D
authors.initials: JD
authors.lastname: Bartlett
mesh_terms: D000565:Ameloblasts; D000566:Amelogenesis; D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic; D003743:Dental Enamel / Q000254:growth & development*; D051379:Mice; D011744:Pyrimidinones; D051176:beta Catenin / Q000502:physiology*
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; C492448:ICG 001; D011744:Pyrimidinones; D051176:beta Catenin
keywords: E-cadherin; cell-cell attachment; enamel; migration; β-catenin