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首页> 外文期刊>Development >The life history of an embryonic signaling center: BMP-4 induces p21 and is associated with apoptosis in the mouse tooth enamel knot.
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The life history of an embryonic signaling center: BMP-4 induces p21 and is associated with apoptosis in the mouse tooth enamel knot.

机译：胚胎信号传导中心的生命史：BMP-4诱导p21并与小鼠牙釉质结中的细胞凋亡相关。

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The enamel knot, a transient epithelial structure, appears at the onset of mammalian tooth shape development. Until now, the morphological, cellular and molecular events leading to the formation and disappearance of the enamel knot have not been described. Here we report that the cessation of cell proliferation in the enamel knot in mouse molar teeth is linked with the expression of the cyclin-dependent kinase inhibitor p21. We show that p21 expression is induced by bone morphogenetic protein 4 (BMP-4) in isolated dental epithelia. As Bmp-4 is expressed only in the underlying dental mesenchyme at the onset of the enamel knot formation, these results support the role of the cyclin-dependent kinase inhibitors as inducible cell differentiation factors in epithelial-mesenchymal interactions. Furthermore, we show that the expression of p21 in the enamel knot is followed by Bmp-4 expression, and subsequently by apoptosis of the differentiated enamel knot cells. Three-dimensional reconstructions of serial sections after in situ hybridization and Tunel-staining indicated an exact codistribution of Bmp-4 transcripts and apoptotic cells. Apoptosis was stimulated by BMP-4 in isolated dental epithelia, but only in one third of the explants. We conclude that Bmp-4 may be involved both in the induction of the epithelial enamel knot, as a mesenchymal inducer of epithelial cyclin-dependent kinase inhibitors, and later in the termination of the enamel knot signaling functions by participating in the regulation of programmed cell death. These results show that the life history of the enamel knot is intimately linked to the initiation of tooth shape development and support the role of the enamel knot as an embryonic signaling center.
机译：釉质结是一种短暂的上皮结构，出现在哺乳动物牙齿形状发展的开始时。到目前为止，尚未描述导致釉质结形成和消失的形态，细胞和分子事件。在这里，我们报道小鼠磨牙牙釉质结中细胞增殖的停止与细胞周期蛋白依赖性激酶抑制剂p21的表达有关。我们显示p21表达是由孤立的牙齿上皮细胞中的骨形态发生蛋白4（BMP-4）诱导的。由于Bmp-4仅在釉质结形成开始时在下面的牙间充质中表达，因此这些结果支持细胞周期蛋白依赖性激酶抑制剂作为上皮-间质相互作用中的可诱导细胞分化因子的作用。此外，我们表明在釉质结中p21的表达是由Bmp-4表达，随后是分化的釉质结细胞的凋亡。原位杂交和Tunel染色后连续切片的三维重建表明Bmp-4转录本和凋亡细胞的精确共分布。 BMP-4刺激孤立的牙齿上皮细胞凋亡，但只有三分之一的外植体细胞凋亡。我们得出结论，Bmp-4可能作为上皮细胞周期蛋白依赖性激酶抑制剂的间充质诱导物参与上皮釉质结的诱导，并随后通过参与程序化细胞的调节而参与釉质结信号传导功能的终止。死亡。这些结果表明，牙釉质结的生活史与牙齿形状的形成密切相关，并支持牙釉质结作为胚胎信号传递中心的作用。

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