Wnt is involved in odontoblast and ameloblast differentiation and matrix protein expression in dentin and enamel, but there have been only a few reports on Axin2 in the Wnt signaling pathway. Axin2 promotes Smad3 activation in the transforming growth factor beta (TGF-ß) signaling pathway, and the presence of crosstalk between the Wnt and TGF-ß signaling pathways has been reported, but there have been no reports on that in odontogenic cells. Thus, we examined immunohistochemically the factors in

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... the 2 signaling pathways using serial sections of rat first molar germ at embryonic day 19 and 10 days after birth to investigate whether there is cross-talk between the 2 signaling pathways through Axin2 and Smad3. Factors in the Wnt signaling pathway: Wnt10, Dishevelled (Dvl), and Axin2, and those in the TGF-ß signaling pathway: TGF-ß receptor 1 (TGF-ß-R1), Smad3, and its active type, phosphorylated Smad3 (p-Smad3), showed similar immunoreactions; in detail, odontoblasts possessing secretory function, rather than dental papilla cells and preodontoblasts, and secretorystage ameloblasts, rather than inner enamel epithelium, showed stronger reactions, whereas the reaction of maturation-stage ameloblasts was very weak. In addition, the reaction of Axin2 was completely consistent with that of pSmad3, and odontoblasts and secretory ameloblasts showed the strongest positive reactions. Accordingly, it was suggested that the TGF-ß signaling pathway as well as Dvl-and Axin2-mediated Wnt10 signaling pathway may are involved in odontoblast and ameloblast differentiation and the secretory function of these cells. In addition, the reaction of Axin2 was completely consistent with that of pSmad3, and odontoblasts and secretory ameloblasts showed the strongest positive reactions, suggesting that a cross-talk between the 2 signaling pathways through Axin2 and Smad3 may be involved in the odontoblast and ameloblast differentiation and secretory function of these cells.