|Title of PhD thesis:|| ||Role of Wnt Signaling in Proliferation and Differentiation of human neural progenitor cells (ReNcell VM)|
|Reviewers:|| ||Arndt Rolfs, University of Rostock, Rostock, Germany|
| ||Dieter G. Weiss, University of Rostock, Rostock, Germany|
| ||Conny Noguchi, National Institutes of Health, Bethesda, USA|
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.
- J. Bäder, R. Hübner, M. Menzel, S. Ortinau, A. Rolfs and J. Frahm (2008): TCF activity and neuronal differentiation of immortalized human neural progenitor cell line (ReNcell VM). - Poster, Berlin, 5th International Stem Cell School.
- R. Hübner, A. Rolfs and J. Frahm (2008): Wnt target genes in human neural progenitor cells. - Poster, Berlin, 5th International Stem Cell School.
- Rayk Hübner, Arndt Rolfs and Jiankai Luo (2009): Influence of Wnt Signaling on Proliferation and Neuronal Differentiation of Human Neural Progenitor Cells. - Poster, Odense, Danmark, 6th International Stem Cells School in Regenerative Medicine .
- Rayk Hübner, Orianne Mazemondet, Jana Frahm, Dirk Koczan, Dieter G. Weiss, Adelinde M. Uhrmacher, Arndt Rolfs and Jiankai Luo (2009): Spatiotemporal regulation of Wnt signaling components in different differentiation stages of human neural progenitor cells. - Poster, Prague, International Stem Cell School in Regenerative Medicine 2009.