Tooth development is accomplished by a series of epithelial-mesenchyme interactions. Epithelial Wnt/β-catenin signaling is sufficient to initiate tooth development by activating Shh, Bmps, Fgfs and Wnts in dental epithelium, which in turn, triggered the expression of odontogenic genes in the underlying mesenchyme. Although constitutive activation of Wnt/β-catenin signaling in oral ectoderm resulted in the continuous tooth formation throughout the life span, if the epithelial Wnt/β-catenin signaling could induce the mesenchyme other than oral mesenchyme still required to be elucidated. In this study, we found that in the K14-cre; Ctnnb1^ex3f mice, the markers of dental epithelium, such as Pitx2, Shh, Bmp2, Fgf4, and Fgf8, were not only activated in the oral ectoderm, but also in the cheek epithelium. Surprisingly, the underlying cheek mesenchymal cells were elongated and expressed Dspp. Further investigations detected that the expression of Msx1 and Runx2 extended from oral to cheek mesenchyme. These findings suggested that epithelial Wnt/β-catenin signaling was capable of inducing Dspp expression in non-dental mesenchyme. Moreover, Dspp expression in the K14-cre; Ctnnb1^ex3f oral mesenchyme was activated earlier than that in the wild type littermates. In contrast, although the elongated oral epithelial cells were detected in the K14-cre; Ctnnb1^ex3f mice, the Amelogenin expression was suppressed. The differential effects of the persistent epithelial Wnt/β-catenin signaling on ameloblast and odontoblast differentiation might result from the altered BMP signaling. In summary, our findings suggested that the epithelial Wnt/β-catenin signaling could induce craniofacial mesenchyme into odontogenic program and promote odontoblast differentiation.

牙齿的发育是通过一系列上皮-间质相互作用完成的。上皮Wnt /β-catenin信号传导足以激活牙齿上皮中的Shh，Bmps，Fgfs和Wnts，从而引发牙齿发育，进而触发潜在的间充质中牙源性基因的表达。尽管口腔外胚层中Wnt /β-catenin信号传导的组成性激活导致整个生命周期中牙齿的连续形成，但是如果上皮Wnt /β-catenin信号传导可以诱导除口腔间充质以外的间充质，则仍需要阐明。在这项研究中，我们发现在K14-cre中；Ctnnb1 ^ex3f小鼠，牙齿上皮的标志物，例如Pitx2，Shh，Bmp2，Fgf4和Fgf8不仅在口腔外胚层中被激活，而且在颊上皮中也被激活。令人惊讶的是，下面的脸颊间充质细胞被拉长并表达了Dspp。进一步的研究发现，Msx1和Runx2的表达从口腔延伸到颊间充质。这些发现表明，上皮Wnt /β-连环蛋白信号传导能够诱导非牙齿间充质中Dspp的表达。而且，Dspp表达在K14-cre中；Ctnnb1 ^ex3f口服间充质比野生型同窝^幼仔更早被激活。相反，尽管在K14-cre中检测到了细长的口腔上皮细胞；Ctnnb1^在ex3f小鼠中， Amelogenin表达受到抑制。持续的上皮Wnt /β-catenin信号传导对成釉细胞和成牙本质细胞分化的不同影响可能是由改变的BMP信号传导引起的。总之，我们的发现表明上皮Wnt /β-catenin信号传导可诱导颅面间充质进入成牙细胞程序并促进成牙本质细胞分化。