Department of Periodontology, Affiliated Stomatological Hospital, Fujian Medical University, Fuzhou, Fujian, China.
Dev Dyn. 2011 Feb;240(2):432-40. doi: 10.1002/dvdy.22550.
Wnt/β-catenin signaling is essential for tooth development beyond the bud stage, but little is known about the role of non-canonical Wnt signaling in odontogenesis. Here we compared the expression of Wnt5a, a representative of noncanonical Wnts, with that of Ror2, the Wnt5a receptor for non-canonical signaling, in the developing tooth, and analyzed tooth phenotype in Wnt5a mutants. Wnt5a-deficient mice exhibit retarded tooth development beginning from E16.5, leading to the formation of smaller and abnormally patterned teeth with a delayed odontoblast differentiation at birth. These defects are associated with upregulated Axin2 and Shh expression in the dental epithelium and reduced levels of cell proliferation in the dental epithelium and mesenchyme. Retarded tooth development and defective odontoblast differentiation were also observed in Ror2 mutant mice. Our results suggest that Wnt5a regulates growth, patterning, and odontoblast differentiation during odontogenesis, at least partially by modulating Wnt/β-catenin canonical signaling.
Wnt/β-catenin 信号通路对于芽期后的牙齿发育至关重要,但关于非经典 Wnt 信号通路在牙齿发生中的作用知之甚少。在这里,我们比较了非经典 Wnt 的代表 Wnt5a 与非经典信号的 Wnt5a 受体 Ror2 在发育中的牙齿中的表达,并分析了 Wnt5a 突变体的牙齿表型。Wnt5a 缺陷型小鼠从 E16.5 开始表现出牙齿发育迟缓,导致出生时形成更小且异常模式的牙齿,牙本质细胞分化延迟。这些缺陷与牙上皮中 Axin2 和 Shh 表达上调以及牙上皮和间充质中细胞增殖减少有关。Ror2 突变型小鼠也观察到牙齿发育迟缓及成牙本质细胞分化缺陷。我们的结果表明,Wnt5a 通过调节 Wnt/β-catenin 经典信号通路,在牙齿发生过程中调节牙齿的生长、形态和牙本质细胞分化。