Cell dynamics in Hertwig's epithelial root sheath are regulated by β-catenin activity during tooth root development.

β-catenin, a key mediator of Wnt signaling, plays multiple roles in tooth development. However, the role of β-catenin in Hertwig's epithelial root sheath (HERS) during root formation remains unclear. In this study, we generated inducible tissue-specific β-catenin conditional knockout mice (Ctnnb1i∆shh ) to investigate how β-catenin in HERS affects tooth root development. The inactivation of β-catenin in HERS led to interrupted root elongation due to premature disruption of HERS. This phenotype was accompanied by reduced cell-cell adhesion and decreased expression of junctional proteins, as well as increased epithelial-to-mesenchymal transition of HERS cells upon β-catenin depletion. Accordingly, stabilization of β-catenin in HERS (Catnbi∆shh ) led to the formation of unfragmented HERS and resulted in the failure of HERS dissociation, with increased expression of junctional proteins. Our results suggest that fine control of β-catenin is important for HERS to guide root formation through regulating its structural integrity.