Department of Craniofacial Development, Dental Institute, King's College London, Guy's Hospital, London, UK.
Eur J Orthod. 2012 Aug;34(4):518-24. doi: 10.1093/ejo/cjr049. Epub 2011 Apr 29.
The correct number and shape of teeth are critical factors for an aesthetic and functional dentition. Understanding the molecular mechanisms regulating tooth number and shape are therefore important in orthodontics. Mice have only one incisor and three molars in each jaw quadrant that are divided by a tooth-less region, the diastema. Although mice lost teeth in the diastema during evolution, the remnants of the evolutionary lost teeth are observed as transient epithelial buds in the wild-type diastema during early stages of development. Shh and Fgf signaling pathways that are essential for tooth development have been shown to be repressed in the diastema. It remains unclear however how Wnt signaling, that is also required for tooth development, is regulated in the diastema. In this study we found that in the embryonic diastema, Wnt5a expression was observed in mesenchyme, whereas Wnt4 and Wnt10b were expressed in epithelium. The expression of Wnt6 and Wnt11 was found in both tissues. The Wnt co-receptor, Lrp6, was weakly expressed in the diastema overlapping with weak Lrp4 expression, a co-receptor that inhibits Wnt signaling. Secreted Wnt inihibitors Dkk1, Dkk2, and Dkk3 were also expressed in the diastema. Lrp4 mutant mice develop supernumerary teeth in the diastema that is accompanied by upregulation of Wnt signaling and Lrp6 expression. Wnt signaling is thus usually attenuated in the diastema by these secreted and membrane bound Wnt inhibitors.
牙齿的正确数量和形状是美观和功能牙列的关键因素。因此，了解调节牙齿数量和形状的分子机制在正畸学中非常重要。小鼠的每一个颌骨象限只有一颗门齿和三颗臼齿，它们之间由一个无牙区域——齿隙分隔。尽管在进化过程中，小鼠在齿隙中失去了牙齿，但在野生型齿隙的早期发育阶段，仍能观察到进化中失去的牙齿的残余物，即短暂的上皮芽。对于牙齿发育至关重要的 Shh 和 Fgf 信号通路在齿隙中被抑制。然而，Wnt 信号通路如何在齿隙中被调节，目前仍不清楚。在这项研究中，我们发现，在胚胎齿隙中，Wnt5a 在间质中表达，而 Wnt4 和 Wnt10b 在上皮中表达。Wnt6 和 Wnt11 的表达存在于两种组织中。Wnt 共受体 Lrp6 在与弱表达的 Lrp4 重叠的齿隙中弱表达，Lrp4 是一种抑制 Wnt 信号的共受体。分泌的 Wnt 抑制剂 Dkk1、Dkk2 和 Dkk3 也在齿隙中表达。Lrp4 突变小鼠在齿隙中会产生多余的牙齿，伴随着 Wnt 信号和 Lrp6 表达的上调。因此，这些分泌的和膜结合的 Wnt 抑制剂通常会在齿隙中减弱 Wnt 信号。
