Abstract：
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;Triofl/fl mice to address the potential function of Trio in tooth development. Wnt1-cre;Triofl/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.
摘要：
三重奏,Rho鸟嘌呤核苷酸交换因子（Rho-GEF），在细胞迁移中起着不同的作用，细胞轴突引导和细胞骨架重组。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GTPasesRhoA和Rac1是Trio的靶分子，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Wnt1-cre;Triofl/fl小鼠，以解决Trio在牙齿发育中的潜在功能。Wnt1-cre;Triofl/fl小鼠显示短根畸形以及牙源性标记如RUNX2，OSX，OCN,OPN。体外，Trio在人牙乳头干细胞（SCAP）中沉默。与对照组相比,实验组的增殖和迁移能力被破坏。在击倒SCAP中的Trio之后，细胞表现为牙源性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p38MAPK通路，发现Trio的缺失阻断了p38MAPK信号的级联转导。总之,我们将Trio确定为调节根系发育的新协调因子,并阐明了其相关的分子事件.
