Albrecht-Kossel-Institute for Neuroregeneration (AKos), School of Medicine, University of Rostock, Gehlsheimer Strasse 20, 18147 Rostock, Germany.
Biochem Biophys Res Commun. 2010 Sep 24;400(3):358-62. doi: 10.1016/j.bbrc.2010.08.066. Epub 2010 Aug 22.
Wnt ligands play pivotal roles in the control of cell growth and differentiation during central nervous system development via the Wnt signaling pathway. In this study, we investigated the effects of Wnt-3a and β-catenin on the differentiation of ReNcell VM human neural progenitor cells. After overexpression of Wnt-3a or mutant-stabilized β-catenin in ReNcell VM cells, their effects on TCF-mediated transcription, Wnt target gene expression and differentiation into neuronal and glial cells were investigated. Our results show that activation of Wnt/β-catenin signaling increases TCF-mediated transcription and the expression of the Wnt target genes Axin2, LEF1 and CyclinD1 in ReNcell VM cells. In contrast to mutant-stabilized β-catenin, Wnt-3a increases neurogenesis during the differentiation of ReNcell VM cells. Thus, our data suggest that neurogenesis induced by Wnt-3a is independent of the transcriptional activity of Wnt/β-catenin pathway in ReNcell VM cells.
Wnt 配体通过 Wnt 信号通路在中枢神经系统发育过程中对细胞生长和分化的控制中发挥关键作用。在这项研究中,我们研究了 Wnt-3a 和 β-连环蛋白对 ReNcell VM 人神经祖细胞分化的影响。在 ReNcell VM 细胞中转染 Wnt-3a 或突变稳定的 β-连环蛋白后,研究了它们对 TCF 介导的转录、Wnt 靶基因表达和向神经元和神经胶质细胞分化的影响。结果表明,Wnt/β-连环蛋白信号的激活增加了 ReNcell VM 细胞中 TCF 介导的转录和 Wnt 靶基因 Axin2、LEF1 和 CyclinD1 的表达。与突变稳定的 β-连环蛋白不同,Wnt-3a 增加了 ReNcell VM 细胞分化过程中的神经发生。因此,我们的数据表明,Wnt-3a 诱导的神经发生与 ReNcell VM 细胞中 Wnt/β-连环蛋白通路的转录活性无关。