Previous studies indicated that the elevated mesenchymal Wnt/β-catenin signaling deprived dental mesenchyme of odontogenic fate. By utilizing ex vivo or pharmacological approaches, Wnt/β-catenin signaling in the developing dental mesenchyme was suggested to suppress the odontogenic fate by disrupting the balance between Axin2 and Runx2. In our study, the Osr2-cre^KI; Ctnnb1^ex3f mouse was used to explore how mesenchymal Wnt/β-catenin signaling suppressed the odontogenic fate in vivo. We found that all of the incisor and half of the molar germs of Osr2-cre^KI; Ctnnb1^ex3fmice started to regress at E14.5 and almost disappeared at birth. The expression of Fgf3 and Msx1 was dramatically down-regulated in the E14.5 Osr2-cre^KI; Ctnnb1^ex3f incisor and molar mesenchyme, while Runx2transcription was only diminished in incisor mesenchyme. Intriguingly, in the E14.5 Osr2-cre^KI; Ctnnb1^ex3f incisor epithelium, the expression of Noggin was activated, while Shh was abrogated. Similarly, the Wnt and BMP antagonists, Ectodin and Noggin were also ectopically activated in the E14.5 Osr2-cre^KI; Ctnnb1^ex3f molar epithelium. Recombination of E13.5 Osr2-cre^KI; Ctnnb1^ex3f molar mesenchyme with E10.5 and E13.5 WT dental epithelia failed to develop tooth. Taken together, the mesenchymal Wnt/β-catenin signaling resulted in the loss of odontogenic fate in vivo not only by directly suppressing odontogenic genes expression but also by inducing Wnt and BMP antagonists in dental epithelium.

先前的研究表明，间充质Wnt /β-catenin信号的升高剥夺了牙齿间充质的牙源性命运。通过利用离体或药理学方法，发展中的牙齿间充质中的Wnt /β-catenin信号传导被建议通过破坏Axin2和Runx2之间的平衡来抑制牙源性命运。在我们的研究中，Osr2-cre ^KI ; Ctnnb1 ^ex3f小鼠用于研究间充质Wnt /β-catenin信号传导如何在体内抑制牙源性命运。我们发现Osr2-cre ^KI的所有门齿和一半磨牙细菌; Ctnnb1 ^ex3f小鼠在E14.5开始消退，出生时几乎消失。表达Fgf3和Msx1在E14.5 Osr2-cre ^KI中显着下调；Ctnnb1 ^ex3f门齿和磨牙间充质，而Runx2转录仅在门齿间质中减少。有趣的是，在E14.5 Osr2-cre ^KI中；Ctnnb1 ^ex3f切牙上皮，Noggin的表达被激活，而Shh被取消。同样，在E14.5 Osr2-cre ^KI中也异位激活了Wnt和BMP拮抗剂Ectodin和Noggin 。Ctnnb1 ^ex3f磨牙上皮。E13.5的重组Osr2-cre ^KI ; 带有^E10.5和E13.5 WT牙齿上皮的Ctnnb1 ^ex3f磨牙间充质未能发育成牙齿。总之，间充质Wnt /β-catenin信号传导不仅通过直接抑制牙源性基因表达，而且还通过在牙齿上皮细胞中诱导Wnt和BMP拮抗剂而导致体内牙源性命运的丧失。