School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Lo Kwee-Seong Integrated Biomedical Sciences Building, Hong Kong SAR, China.
Division of Surgery, Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas M.D. Anderson Cancer Center, T4.3908, 1515 Holcombe Boulevard, Houston, TX, 77030, USA.
Cell Tissue Res. 2020 Sep;381(3):493-508. doi: 10.1007/s00441-020-03237-2. Epub 2020 Jun 30.
Dab2 is an adaptor protein and a tumor suppressor. Our previous study has found that Dab2 was expressed in early differentiating skeletal muscles in mouse embryos. In this study, we determined the role of Dab2 in the skeletal muscle differentiation using C2C12 myoblasts in vitro and Xenopus laevis embryos in vivo. The expression of Dab2 was increased in C2C12 myoblasts during the formation of myotubes in vitro. Knockdown of Dab2 expression in C2C12 myoblasts resulted in a reduction of myotube formation, whereas the myotube formation was enhanced upon overexpression of Dab2. Re-expression of Dab2 in C2C12 myoblasts with downregulated expression of Dab2 restored their capacity to form myotubes. Microarray profiling and subsequent network analyses on the 155 differentially expressed genes after Dab2 knockdown showed that Mef2c was an important myogenic transcription factor regulated by Dab2 through the p38 MAPK pathway. It was also involved in other pathways that are associated with muscular development and functions. In Xenopus embryos developed in vivo, XDab2 was expressed in the myotome of somites where various myogenic markers were also expressed. Knockdown of XDab2 expression with antisense morpholinos downregulated the expression of myogenic markers in somites. In conclusion, this study is the first to provide solid evidence to show that Dab2 is a positive regulator of the early myoblast differentiation.
Dab2 是一种衔接蛋白和肿瘤抑制因子。我们之前的研究发现，Dab2 在小鼠胚胎早期分化的骨骼肌中表达。在这项研究中，我们使用体外的 C2C12 成肌细胞和体内的非洲爪蟾胚胎来确定 Dab2 在骨骼肌分化中的作用。在体外形成肌管的过程中，Dab2 在 C2C12 成肌细胞中的表达增加。Dab2 表达的敲低导致肌管形成减少，而过表达 Dab2 则增强了肌管形成。在 Dab2 表达下调的 C2C12 成肌细胞中重新表达 Dab2 恢复了它们形成肌管的能力。对 Dab2 敲低后 155 个差异表达基因进行的微阵列分析和随后的网络分析表明，Mef2c 是一个重要的肌源性转录因子，通过 p38 MAPK 途径受 Dab2 调控。它还参与与肌肉发育和功能相关的其他途径。在体内发育的非洲爪蟾胚胎中，XDab2 在体节的肌节中表达，各种肌源性标记物也在那里表达。用反义 morpholino 敲低 XDab2 表达会下调体节中肌源性标记物的表达。总之，这项研究首次提供了确凿的证据，表明 Dab2 是早期成肌细胞分化的正调控因子。
