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Wnt Signal Pathways and Neural Stem Cell Differentiation

Authors: Arndt Rolfs; Katja Rateitschak; Eilhard Mix; Christian Lange;

Wnt Signal Pathways and Neural Stem Cell Differentiation

Abstract

Self-renewal, migration and differentiation of neural progenitor cells are controlled by a variety of pleiotropic signal molecules. Members of the morphogen family of Wnt molecules play a crucial role for developmental and repair mechanisms in the embryonic and adult nervous system. A strategy of disclosure of the role of different canonical (glycogen synthase kinase-3β/β-catenin-dependent) and noncanonical (Ca<sup>2+</sup>- and JNK-dependent) signal pathways for progenitor cell expansion and differentiations is illustrated at the example of the rat striatal progenitor cell line ST14A that is immortalized by stable retroviral transfection with a temperature-sensitive mutant of the SV40 large T antigen. A shift from permissive 33°C to nonpermissive 39°C leads to proliferation stop and start of differentiation into glial and neuronal cells. Investigation of expression of Wnts, Wnt receptors and Wnt-dependent signal pathway assay point to a stage-dependent involvement of canonical and noncanonical signaling in proliferation and differentiation of ST14A cells, whereby a mutual suppression of pathway activities is likely. Canonical Wnt molecules are not detected in proliferating and differentiating ST14A cells except Wnt2. The noncanonical Wnt molecules Wnt4, Wnt5a and Wnt11 are expressed in proliferating cells and increase during differentiation, whereas cellular β-catenin decreases in the early phase and is restored in the late phase of differentiation. Accumulation of β-catenin at the membrane in undifferentiated proliferating cells and its nuclear localization in nondividing undifferentiated cells under differentiation conditions argues for a distinct spatially regulated role of the molecule in the proliferation and early differentiation phase. Ca<sup>2+</sup>-dependent and JNK-dependent noncanonical Wnt signaling is not detected during differentiation of ST14A cells. Complete exploration of the role of Wnt pathways, for differentiation of the neural progenitor cells ST14A will require Wnt overexpression and exposure of ST14A cells to exogenous Wnts either with purified Wnts or by co-cultures with Wnt producers.

Related Organizations
Keywords

Neurons, Wnt Proteins, Stem Cells, Animals, Humans, Cell Differentiation, Nervous System, Signal Transduction

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
67
Top 10%
Top 10%
Top 10%
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