Wnt signaling plays an essential role in the tooth morphogenesis of the dental epithelium and mesenchyme. However, it remains unclear if Wnt ligands, produced from dental mesenchyme, are necessary for odontoblast differentiation and dentin formation. To address the role of Wnt signalling in odontoblast differentiation and dentin formation, we analysed odontoblast-specific Wntless (Wls), a chaperon protein that regulates Wnt sorting and secretion, conditional knockout mice. Odontoblast-specific disruption of Wls leads to severe defects in dentin formation and root elongation. Dentin thickness decreased apparently and pulp chambers enlarged in the mandibular molars of mutant mice. Although the initial odontoblast differentiation was normal in the mutant, odontoblasts became cuboidal and dentin thickness was reduced. In immunohistochemistry, Wnt10a, β-catenin, type I collagen, and dentin sialoprotein were significantly down-regulated in the mutant odontoblasts. In addition, roots were short and root canals were widened. Cell proliferation was reduced in the developing root apex of mutant molars. Furthermore, Axin2 and Osx expression was remarkably decreased in mutant odontoblasts. Deletion of the Wls gene in odontoblasts inhibits odontoblast maturation and root elongation. These results indicate that Wnt ligands produced in odontoblasts are required for dentin apposition and root elongation.
Disclosure: The authors declared no competing interests. This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (No. 2013R1A2A1A01007642).