The role of Rho-GEF Trio in regulating tooth root development through the p38 MAPK pathway
The role of Rho-GEF Trio in regulating tooth root development through the p38 MAPK pathway
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Rho-GEF Trio 通过 p38 MAPK 通路调节牙根发育的作用
DOI：
10.1016/j.yexcr.2018.09.022
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发表时间：
2018-11-15
影响因子：
3.7
通讯作者：
Ma, Junqing
中科院分区：
文献类型：
--
作者：
Chen, Huimin;Guo, Shuyu;Ma, Junqing
Trio是Rho鸟嘌呤核苷酸交换因子（Rho-GEF），在细胞迁移、细胞轴突导向和细胞骨架重组中起着多种作用。在进化过程中保守，Trio编码两个鸟嘌呤核苷酸交换因子结构域（GEF）并激活小GTP酶。Rho家族小GTP酶RhoA和Rac 1是Trio的靶分子，已被描述参与颅面发育和牙齿形成。然而，Trio在牙齿发育中的确切作用仍然难以捉摸。在这项研究中，我们产生了Wnt 1-cre;Trio（fl/fl）小鼠，以解决Trio在牙齿发育中的潜在功能。Wnt 1-cre;Trio（fl/fl）小鼠表现出短根畸形以及牙源性标记物如RUNX 2、OSX、OCN和OPN的表达降低。在体外实验中，Trio在人牙乳头干细胞（SCAPs）中被沉默。与对照组相比，实验组细胞增殖和迁移能力受到干扰。敲除SCAPs中的Trio后，细胞表现出牙向分化差和矿化结节弱的表型。为了研究潜在的机制，我们研究了p38 MAPK通路，发现Trio的缺失阻断了p38 MAPK信号的级联转导。综上所述，我们确定了Trio作为一种新的协调剂，在调节根的发展，并阐明了其相关的分子事件。
Trio, the Rho guanine nucleotide exchange factor (Rho-GEF), plays diverse roles in cell migration, cell axon guidance and cytoskeleton reorganization. Conserved during evolution, Trio encodes two guanine nucleotide exchange factor domains (GEFs) and activates small GTPases. The Rho-family small GTPases RhoA and Rac1, which are target molecules of Trio, have been described to engage in craniofacial development and tooth formation. However, the exact role of Trio in tooth development remains elusive. In this study, we generated Wnt1-cre;Trio(fl/fl) mice to address the potential function of Trio in tooth development. Wnt1-cre;Trio(fl/fl) mice showed short root deformity as well as decreased expression of odontogenic makers such as RUNX2, OSX, OCN, and OPN. In vitro, Trio was silenced in human stem cells of dental papilla (SCAPs). Compared with the control group, the proliferation and migration ability in the experimental group was disrupted. After knocking down Trio in SCAPs, the cells showed phenotypes of poor odontogenic differentiation and weak mineralized nodules. To study the underlying mechanism, we investigated the p38 MAPK pathway and found that loss of Trio blocked the cascade transduction of p38 MAPK signaling. In conclusion, we identified Trio as a novel coordinator in regulating root development and clarified its relevant molecular events.