The aim of this study was to shed light on the poorly understood network of signaling pathways which are responsible for the cell fate determination and differentiation of human neural progenitor cells initiated by Wnt-3a treatment and Notch pathway inhibition.
Wnt-3a was not only able to induce the β-catenin dependent Wnt pathway, but also regulated the Notch target genes HES1 and HES5.This regulation was independent of the β-catenin dependent pathway, because it was independent of GSK3β inhibition, independent of the formation of a Wnt-3a-LRP6-Frizzled receptor complex and independent of the inhibition of the BMP signaling pathway which is known to be initiated by Wnt ligands through β-catenin.
In sum, the combined treatment with Wnt-3a and DAPT (Notch inhibitor) and the thereout resulting increase of cells positive for neuronal markers and decrease of stemness marker is an outstanding step forward to drive NPCs from an undifferentiated state to neurons instead of glial cells which is a prerequisite for cell based therapies utilizing neuronal cells.