In mouse, continuous growth of the postnatal incisor is coordinated by two populations of multipotent progenitor cells, the dental papilla mesenchymal cells and dental epithelial stem cells, residing at the proximal end of the incisor, yet the molecular mechanism underlying the cooperation between mesenchymal and epithelial cells is largely unknown. Here, transforming growth factor‐β (TGF‐β) type II receptor (Tgfbr2) was specifically deleted within the postnatal dental papilla mesenchyme. The Tgfbr2‐deficient mice displayed malformed incisors with wavy mineralized structures at the labial side as a result of increased differentiation of dental epithelial stem cells. We found that mesenchymal Tgfbr2 disruption led to upregulated expression of Wnt5a and downregulated expression of Fgf3/10 in the mesenchyme, both of which synergistically enhanced Lrp5/6‐β‐catenin signaling in the cervical loop epithelium. In accord with these findings, mesenchyme‐specific depletion of the Wnt transporter gene Wls abolished the aberrant mineralized structures caused by Tgfbr2 deletion. Thus, mesenchymal TGF‐β signaling provides a unifying mechanism for the homeostasis of dental epithelial stem cells via a Wnt signaling‐mediated mesenchymal‐epithelial cell interaction. Stem Cells 2014;32:2939–2948

中文翻译：

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间充质 TGF-β 信号通路通过 Wnt 信号通路协调牙齿上皮干细胞稳态

在小鼠中，出生后切牙的持续生长由位于切牙近端的两个多能祖细胞群，即牙乳头间充质细胞和牙上皮干细胞协调，但间充质和上皮之间合作的分子机制细胞在很大程度上是未知的。在这里，转化生长因子-β（TGF-β）II 型受体（Tgfbr2）在出生后牙乳头间充质中被特异性删除。由于牙齿上皮干细胞的分化增加，Tgfbr2缺陷小鼠在唇侧显示出具有波浪状矿化结构的畸形门牙。我们发现间充质 Tgfbr2 破坏导致间充质中 Wnt5a 的表达上调和 Fgf3/10 的表达下调，这两者协同增强了宫颈袢上皮中的 Lrp5/6-β-catenin 信号传导。根据这些发现，Wnt 转运蛋白基因 Wls 的间充质特异性缺失消除了由 Tgfbr2 缺失引起的异常矿化结构。因此，间充质 TGF-β 信号通过 Wnt 信号介导的间充质-上皮细胞相互作用为牙齿上皮干细胞的稳态提供了统一的机制。干细胞 2014；32：2939–2948 间充质 TGF-β 信号通过 Wnt 信号介导的间充质-上皮细胞相互作用为牙齿上皮干细胞的稳态提供了统一的机制。干细胞 2014；32：2939–2948 间充质 TGF-β 信号通过 Wnt 信号介导的间充质-上皮细胞相互作用为牙齿上皮干细胞的稳态提供了统一的机制。干细胞 2014；32：2939–2948