Intra-epithelial Requirement of Canonical Wnt Signaling for Tooth Morphogenesis

• Published in: The Journal of biological chemistry Vol. 288; no. 17; pp. 12080 - 12089
• Main Authors: Zhu, XiaoJing, Zhao, Pan, Liu, YuDong, Zhang, XiaoYun, Fu, Jiang, Ivy Yu, H.-M., Qiu, Mengsheng, Chen, YiPing, Hsu, Wei, Zhang, Zunyi
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 26-04-2013; American Society for Biochemistry and Molecular Biology
• Subjects: Animals; Dental Enamel - cytology; Dental Enamel - embryology; Developmental Biology; Enamel Knot; Epithelium; Epithelium - embryology; Gene Expression Regulation, Developmental - physiology; Gene Knockout; Gpr177; Intra-epithelial Signaling; Intracellular Signaling Peptides and Proteins - genetics; Intracellular Signaling Peptides and Proteins - metabolism; Mice; Mice, Transgenic; Organogenesis - physiology; Receptors, G-Protein-Coupled - genetics; Receptors, G-Protein-Coupled - metabolism; Secretion; Tooth Development; Tooth Morphogenesis; Wnt; Wnt Proteins - genetics; Wnt Proteins - metabolism; Wnt Signaling; Wnt Signaling Pathway - physiology; Wnt Signaling; Tooth Development; Enamel Knot; Secretion; Intra-epithelial Signaling; Gene Knockout; Epithelium; Wnt; Gpr177; Tooth Morphogenesis
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M113.462473

Multiple Wnt ligands are expressed in the developing tooth and play important and redundant functions during odontogenesis. However, the source of Wnt ligands and their targeting cells and action mechanism in tooth organogenesis remain largely elusive. Here we show that epithelial inactivation of Gpr177, the mouse Wntless (Wls) whose product regulates Wnt sorting and secretion, leads to arrest of tooth development at the early cap stage and abrogates tooth-forming capability of the dental epithelium. Gpr177 in the epithelium is necessary for the activation of canonical Wnt signaling in the dental epithelium and formation of a functional enamel knot. Epithelial deletion of Gpr177 results in defective gene expression and cellular behavior in the dental epithelium but does not alter odontogenic program in the mesenchyme. Furthermore, deletion of Axin2, a negative intracellular regulator of canonical Wnt signaling, rescues the tooth defects in mice carrying Gpr177 mutation in the dental epithelium. Together with the fact that active Wnt canonical signaling is present predominantly in the dental epithelium during tooth development, our results demonstrate that Gpr177-mediated Wnt ligands in the dental epithelium act primarily in an intra-epithelial context to regulate enamel knot formation and subsequent tooth development.
Background: Multiple Wnts are expressed and play an important role in tooth development.
Results: Inactivation of Gpr177 in dental epithelium leads to inhibition of Wnt signaling activity and arrest of early tooth development.
Conclusion: Intra-epithelial action of Wnt signaling is essential for early tooth development.
Significance: Dental epithelium is the primary target of epithelial-derived Wnts during tooth development.