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 beta-catenin on the differentiation of ReNcell VM human neural progenitor cells After overexpression of Wnt-3a or mutant-stabilized beta-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/beta-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 beta-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/beta-catenin pathway in ReNcell VM cells. (C) 2010 Elsevier Inc All rights reserved