Synopsis

Apoptosis is known to be an essential mechanism for eliminating redundant cells during CNS development. The proliferation and differentiation of neural progenitor cells are accompanied by massive apoptotic cell death and the canonical Wnt-signaling pathway-driven differentiation of neural progenitor cells is presumed to interfere with apoptosis pathways as well. However, the molecular interlock between the canonical Wnt pathway and apoptotic pathways is still unknown.

The aim of PhD work was to study the molecular mechanisms of apoptotic processes during the differentiation process of the human neural VM197 progenitor cell line in vitro. Expression levels of apoptosis relevant proteins were quantified in time series by Western/Immunoblotting in respect to their amount and activation state and gene expressions were determined based on DNA-microarrays and qRT-PCR studies.

Results of PhD work show that the human neural VM197 progenitor cell line is a suitable model to investigate the role of apoptosis pathways involved in the canonical Wnt pathway-driven development of undifferentiated neural precursor cells into differentiated neuronal cell types, like neurons and glial cells. The differentiation process of these cells was accompanied by an activation of pro- as well as anti-apoptotic components of the extrinsic and intrinsic apoptosis signaling pathway in a time dependent manner and an increase of apoptotic loss of cells. Differentiated cells were characterized by a diminished apoptotic susceptibility compared to proliferating cells. β-catenin cleavage and a significantly decreased apoptosis rate after the inhibition of GSK-3β in differentiated cells indicate an interconnectivity of proteins of the canonical Wnt signaling pathway and apoptotic signaling cascades.

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