Epithelial Is Essential for Tooth Root Furcation Morphogenesis.

(Wingless-type MMTV integration site family, member 10A) plays a crucial role in tooth development, and patients with biallelic mutation and mice lacking show taurodontism. However, whether epithelial or mesenchymal controls the initiation of the root furcation formation remains unclear, and the functional significance of in regulating root morphogenesis has not been clarified. Here, we investigated how affects tooth root development by generating different tissue-specific conditional knockout mice. knockout in the whole tissue () and in dental epithelium () led to an absence of or apically located root furcation in molars of mice, a phenotype that resembled taurodontism. An RNAscope analysis showed that the dynamic epithelial and mesenchymal expression pattern occurred during root development. Immunofluorescent staining of E-cadherin and EdU revealed decreased epithelial cell proliferation at the cervical region of the molar in mice at postnatal day 0 (PN0), just before the initiation of root morphogenesis. Interestingly, we found increased pulpal mesenchymal cell proliferation in the presumptive root furcating region of the molar in mice at PN4 and PN7. RNA-seq indicated that among the Wnt ligands with high endogenous expression levels in molars, was increased after epithelial knockout of . The RNAscope assay confirmed that the expression of and in the dental papilla of the presumptive root furcating region, where dental pulp overgrowth occurred, was increased in molars. Furthermore, after suppression of the elevated level in molars by shRNA adenovirus and kidney capsule grafts, the root furcation defect was partially rescued. Taken together, our study provides the first in vivo evidence that epithelial guides root furcation formation and plays a crucial role in controlling the organized proliferation of adjacent mesenchymal cells by regulating proper expression during root furcation morphogenesis.