Ras Signaling Regulates Stem Cells and Amelogenesis in the Mouse Incisor
Ras Signaling Regulates Stem Cells and Amelogenesis in the Mouse Incisor
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DOI：
10.1177/0022034517717255
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发表时间：
2017-06
影响因子：
7.6
通讯作者：
X. Zheng;X. Zheng;A. Goodwin;H. Tian;A. Jheon;O. Klein
中科院分区：
文献类型：
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作者：
X. Zheng;X. Zheng;A. Goodwin;H. Tian;A. Jheon;O. Klein
Ras信号在牙齿发育过程中的作用知之甚少。Ras蛋白通过多种上游途径激活，包括受体酪氨酸激酶，并通过多种效应物，如丝裂原活化蛋白激酶（MAPK）和PI3K途径传递信号。在此，我们利用小鼠切牙作为模型来研究MAPK和PI3K通路如何调节牙上皮干细胞和釉质发生。啮齿类动物的门牙，由于上皮和间充质干细胞的存在，在动物的整个生命周期中不断生长，为外胚层器官更新和再生的研究提供了一个模型。利用Ras失调模型以及MAPK和PI3K通路的抑制剂，我们发现MAPK和PI3K调节小鼠切牙中的牙上皮干细胞活性、过渡放大细胞增殖和釉质形成。
The role of Ras signaling during tooth development is poorly understood. Ras proteins—which are activated by many upstream pathways, including receptor tyrosine kinase cascades—signal through multiple effectors, such as the mitogen-activated protein kinase (MAPK) and PI3K pathways. Here, we utilized the mouse incisor as a model to study how the MAPK and PI3K pathways regulate dental epithelial stem cells and amelogenesis. The rodent incisor—which grows continuously throughout the life of the animal due to the presence of epithelial and mesenchymal stem cells—provides a model for the study of ectodermal organ renewal and regeneration. Utilizing models of Ras dysregulation as well as inhibitors of the MAPK and PI3K pathways, we found that MAPK and PI3K regulate dental epithelial stem cell activity, transit-amplifying cell proliferation, and enamel formation in the mouse incisor.