Synopsis

The Wnt/β-catenin pathway is known to be involved in neural stem cell self-renewal and neuronal differentiation. Further understanding of this neurogenesis is a prerequisite of cell replacement therapies in neurodegenerative diseases such as Parkinson’s disease. In this context, the role of Wnt/β-catenin signaling was studied in this thesis. The results presented herein indicate that Wnt/β-catenin signaling: (1) is directly connected with the degree of neuronal differentiation in ReNcell VM. (2) -activity includes a mechanism controlling the kinetics of nuclear β-catenin import. (3) -activation affects neurons stronger than non-neurons during the time of fate commitment. (4) mediates cell cycle exit or re-entry and, hence, influences the number of proliferating cells that are committed to the neuronal lineage already (5) increases during dopaminergic differentiation which was shown for the first time both in vitro and in vivo. This study substantiates the presently limited knowledge about neurogenesis in human cell models and closes the gap between the mechanistic knowledge based on rodent models and the use of human neural stem cells for cell replacement strategies in neurodegenerative diseases.

Important publications