Smad4-Shh-Nfic signaling cascade-mediated epithelial-mesenchymal interaction is crucial in regulating tooth root development.
Smad4-Shh-Nfic signaling cascade-mediated epithelial-mesenchymal interaction is crucial in regulating tooth root development.
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DOI：
10.1359/jbmr.091103
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发表时间：
2010-05
期刊：
影响因子：
--
通讯作者：
Chai Y
中科院分区：
文献类型：
--
作者：
Huang X;Xu X;Bringas P Jr;Hung YP;Chai Y
转化生长因子β (TGF-β)/骨形态发生蛋白（BMP）信号在器官发生过程中调节上皮-间质相互作用至关重要，而典型的Smad通路介导的TGF-β/BMP信号在发育和疾病过程中发挥重要作用。在牙齿发育过程中，被称为Hertwig上皮根鞘（HERS）的牙上皮细胞参与了冠发育后的根形成。然而，HERS在调节根发育中的功能意义尚不清楚。在这项研究中，我们研究了Smad4的信号传导机制，Smad4是TGF-β/BMP信号传导的常见Smad，在HERS调控根发育中的作用。Smad4在HERS中组织特异性失活导致K14-Cre中牙釉质和牙本质形成异常；Smad4fl / fl老鼠。在没有Smad4的情况下，HERS会扩大，但不能拉长以引导根的发育。在分子水平上，smad4介导的TGF-β/BMP信号是Shh在HERS中的表达和Nfic（核因子Ic）在颅神经嵴（CNC）来源的牙间质中的表达所必需的。Nfic对牙根发育至关重要，Nfic的缺失会导致类似于K14-Cre的cnc衍生的牙本质缺陷；Smad4fl / fl老鼠。值得注意的是，我们发现异位Shh诱导牙间质Nfic表达，并在一定程度上挽救了K14-Cre的根发育；Smad4fl / fl老鼠。综上所述，我们的研究揭示了一个重要的信号机制，TGF-β/BMP信号依赖于smad依赖的机制，通过Shh信号调节Nfic表达来控制根的发育。HERS与cnc衍生的牙间质之间的相互作用可能指导牙根的大小、形状和数量。©2010美国骨与矿物研究学会。
Transforming growth factor β (TGF-β)/bone morphogenetic protein (BMP) signaling is crucial for regulating epithelial-mesenchymal interaction during organogenesis, and the canonical Smad pathway–mediated TGF-β/BMP signaling plays important roles during development and disease. During tooth development, dental epithelial cells, known as Hertwig's epithelial root sheath (HERS), participate in root formation following crown development. However, the functional significance of HERS in regulating root development remains unknown. In this study we investigated the signaling mechanism of Smad4, the common Smad for TGF-β/BMP signaling, in HERS in regulating root development. Tissue-specific inactivation of Smad4 in HERS results in abnormal enamel and dentin formation in K14-Cre;Smad4fl/fl mice. HERS enlarges but cannot elongate to guide root development without Smad4. At the molecular level, Smad4-mediated TGF-β/BMP signaling is required for Shh expression in HERS and Nfic (nuclear factor Ic) expression in the cranial neural crest (CNC)-derived dental mesenchyme. Nfic is crucial for root development, and loss of Nfic results in a CNC-derived dentin defect similar to the one of K14-Cre;Smad4fl/fl mice. Significantly, we show that ectopic Shh induces Nfic expression in dental mesenchyme and partially rescues root development in K14-Cre;Smad4fl/fl mice. Taken together, our study has revealed an important signaling mechanism in which TGF-β/BMP signaling relies on a Smad-dependent mechanism in regulating Nfic expression via Shh signaling to control root development. The interaction between HERS and the CNC-derived dental mesenchyme may guide the size, shape, and number of tooth roots. © 2010 American Society for Bone and Mineral Research.
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