Manipulating Wnt signaling at different subcellular levels affects the fate of neonatal neural stem/progenitor cells
Language English Country Netherlands Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
27659965
DOI
10.1016/j.brainres.2016.09.026
PII: S0006-8993(16)30654-0
Knihovny.cz E-resources
- Keywords
- Gliogenesis, Ion channel, Neonatal mouse, Neurogenesis, Patch-clamp technique, β-catenin signaling,
- MeSH
- beta Catenin genetics metabolism MeSH
- Immunohistochemistry MeSH
- Cells, Cultured MeSH
- Membrane Potentials physiology MeSH
- Patch-Clamp Techniques MeSH
- Intercellular Signaling Peptides and Proteins genetics metabolism MeSH
- Brain cytology metabolism MeSH
- Mice, Transgenic MeSH
- Neural Stem Cells cytology metabolism MeSH
- Neurogenesis physiology MeSH
- Neuroglia cytology metabolism MeSH
- Neurons cytology metabolism MeSH
- Wnt Signaling Pathway physiology MeSH
- Transcription Factor 4 MeSH
- Basic Helix-Loop-Helix Leucine Zipper Transcription Factors genetics metabolism MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- beta Catenin MeSH
- CTNNB1 protein, mouse MeSH Browser
- Dkk1 protein, mouse MeSH Browser
- Intercellular Signaling Peptides and Proteins MeSH
- Tcf4 protein, mouse MeSH Browser
- Transcription Factor 4 MeSH
- Basic Helix-Loop-Helix Leucine Zipper Transcription Factors MeSH
The canonical Wnt signaling pathway plays an important role in embryogenesis, and the establishment of neurogenic niches. It is involved in proliferation and differentiation of neural progenitors, since elevated Wnt/β-catenin signaling promotes differentiation of neural stem/progenitor cells (NS/PCs1) towards neuroblasts. Nevertheless, it remains elusive how the differentiation program of neural progenitors is influenced by the Wnt signaling output. Using transgenic mouse models, we found that in vitro activation of Wnt signaling resulted in higher expression of β-catenin protein and Wnt/β-catenin target genes, while Wnt signaling inhibition resulted in the reverse effect. Within differentiated cells, we identified three electrophysiologically and immunocytochemically distinct cell types, whose incidence was markedly affected by the Wnt signaling output. Activation of the pathway suppressed gliogenesis, and promoted differentiation of NS/PCs towards a neuronal phenotype, while its inhibition led to suppressed neurogenesis and increased counts of cells of glial phenotype. Moreover, Wnt signaling hyperactivation resulted in an increased incidence of cells expressing outwardly rectifying K+ currents, together with inwardly rectifying Na+ currents, a typical current pattern of immature neurons, while blocking the pathway led to the opposite effect. Taken together, our data indicate that the Wnt signaling pathway orchestrates neonatal NS/PCs differentiation towards cells with neuronal characteristics, which might be important for nervous tissue regeneration during central nervous system disorders. Furthermore, the transgenic mouse strains used in this study may serve as a convenient tool to manipulate β-catenin-dependent signaling in neural progenitors in the neonatal brain.
References provided by Crossref.org
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