Continuous tooth generation in mouse is induced by activated epithelial Wnt/β-catenin signaling
Continuous tooth generation in mouse is induced by activated epithelial Wnt/β-catenin signaling
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DOI：
10.1073/pnas.0607289103
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发表时间：
2006-12-05
影响因子：
11.1
通讯作者：
Thesleff, Irma
中科院分区：
文献类型：
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作者：
Jarvinen, Elina;Salazar-Ciudad, Isaac;Thesleff, Irma
从乳牙到恒牙的单次替换使得哺乳动物的牙齿不同于大多数非哺乳动物脊椎动物的牙齿以及毛发和羽毛等其他上皮器官，后者的持续替换与Wnt信号传导有关。在此我们表明，上皮细胞中表达稳定的β - 连环蛋白的小鼠牙蕾会发育出数十颗牙齿。然而，磨牙牙冠通常是简化的单尖锥体。我们证明，多余的牙齿是通过一种更新过程发育的，在这个过程中，新的信号中心——釉结从现有的牙上皮中萌出。通过提高激活剂产生的内在水平，用一个关于牙齿发育的计算机模型可以重现这种不受限制的牙齿更新的基本方面，这支持了β - 连环蛋白通路作为釉结形成的上游激活剂的作用。这些结果可能暗示Wnt信号传导在牙齿更新中起作用，而当哺乳动物进化出越来越复杂的牙齿形状时，这种更新能力几乎丧失了。
The single replacement from milk teeth to permanent teeth makes mammalian teeth different from teeth of most nonmammalian vertebrates and other epithelial organs such as hair and feathers, whose continuous replacement has been linked to Wnt signaling. Here we show that mouse tooth buds expressing stabilized beta-catenin in epithelium give rise to dozens of teeth. The molar crowns, however, are typically simplified unicusped cones. We demonstrate that the supernumerary teeth develop by a renewal process where new signaling centers, the enamel knots, bud off from the existing dental epithelium. The basic aspects of the unlocked tooth renewal can be reproduced with a computer model on tooth development by increasing the intrinsic level of activator production, supporting the role of P-catenin pathway as an upstream activator of enamel knot formation. These results may implicate Wnt signaling in tooth renewal, a capacity that was all but lost when mammals evolved progressively more complicated tooth shapes.