title: Quantitative and kinetic profile of Wnt/β-catenin signaling components during human neural progenitor cell differentiation.
abstract: ReNcell VM is an immortalized human neural progenitor cell line with the ability to differentiate in vitro into astrocytes and neurons, in which the Wnt/β-catenin pathway is known to be involved. However, little is known about kinetic changes of this pathway in human neural progenitor cell differentiation. In the present study, we provide a quantitative profile of Wnt/β-catenin pathway dynamics showing its spatio-temporal regulation during ReNcell VM cell differentiation. We show first that T-cell factor dependent transcription can be activated by stabilized β-catenin. Furthermore, endogenous Wnt ligands, pathway receptors and signaling molecules are temporally controlled, demonstrating changes related to differentiation stages. During the first three hours of differentiation the signaling molecules LRP6, Dvl2 and β-catenin are spatio-temporally regulated between distinct cellular compartments. From 24 h onward, components of the Wnt/β-catenin pathway are strongly activated and regulated as shown by mRNA up-regulation of Wnt ligands (Wnt5a and Wnt7a), receptors including Frizzled-2, -3, -6, -7, and -9, and co-receptors, and target genes including Axin2. This detailed temporal profile of the Wnt/β-catenin pathway is a first step to understand, control and to orientate, in vitro, human neural progenitor cell differentiation.
authors.affiliation: Albrecht-Kossel-Institute for Neuroregeneration, Centre for Mental Health Disease, University of Rostock, Gehlsheimer Strasse 20, 18147, Rostock, Germany.
authors.forename: Orianne
authors.initials: O
authors.lastname: Mazemondet
authors.forename: Rayk
authors.initials: R
authors.lastname: Hubner
authors.forename: Jana
authors.initials: J
authors.lastname: Frahm
authors.forename: Dirk
authors.initials: D
authors.lastname: Koczan
authors.forename: Benjamin M
authors.initials: BM
authors.lastname: Bader
authors.forename: Dieter G
authors.initials: DG
authors.lastname: Weiss
authors.forename: Adelinde M
authors.initials: AM
authors.lastname: Uhrmacher
authors.forename: Moritz J
authors.initials: MJ
authors.lastname: Frech
authors.forename: Arndt
authors.initials: A
authors.lastname: Rolfs
authors.forename: Jiankai
authors.initials: J
authors.lastname: Luo
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism*; D060466:Axin Protein / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D000072261:Dishevelled Proteins; D051157:Frizzled Receptors / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D060488:Low Density Lipoprotein Receptor-Related Protein-6 / Q000235:genetics / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000473:pathology / Q000628:therapy*; D055495:Neurogenesis / Q000235:genetics*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D015398:Signal Transduction / Q000235:genetics; D033581:Stem Cell Transplantation / Q000379:methods*; D051820:TCF Transcription Factors / Q000235:genetics / Q000378:metabolism; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism; D000071818:Wnt-5a Protein; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: C491761:AXIN2 protein, human; D048868:Adaptor Proteins, Signal Transducing; D060466:Axin Protein; C000606581:DVL2 protein, human; D000072261:Dishevelled Proteins; D051157:Frizzled Receptors; C555475:LRP6 protein, human; D060488:Low Density Lipoprotein Receptor-Related Protein-6; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D051820:TCF Transcription Factors; C085389:WNT5A protein, human; C092778:WNT7A protein, human; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; D051176:beta Catenin