Synopsis

In the Wnt/β-catenin signaling pathway, β-catenin is stabilized upon binding of a Wnt ligand to a receptor. Stabilized β-catenin in turn acts as a transcriptional coactivator to activate expression of target genes thus influencing proliferation and differentiation of neural progenitor cells. However, little is known about the influence of this signaling pathway in the human system. For investigation, the human, fetal neural progenitor cell line ReNcell VM was used as a model system. Quantitative expression analyses revealed a temporally regulated expression of Wnt ligands, receptors and target genes during throughout the differentiation process. Analyses on protein level, reporter gene analyses as well as quantitative expression analyses of target genes clearly show that the cells are able to secrete active Wnt ligands and to transduce a Wnt/β-catenin signal. Activation of Wnt/β-catenin signaling did not increase proliferation. For example, Wnt-3a was able to repress proliferation. In contrast to Wnt-3a which promoted neuronal differentiation without affecting glial differentiation, stabilized β-catenin did not exhibit any effect. In summary, results clearly show that Wnt/β-catenin signaling promotes neuronal differentiation of ReNcell VM cells independently of the transcriptional activity of β-catenin.

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