Manipulating Wnt signaling at different subcellular levels affects the fate of neonatal neural stem/progenitor cells
Jazyk angličtina Země Nizozemsko Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
27659965
DOI
10.1016/j.brainres.2016.09.026
PII: S0006-8993(16)30654-0
Knihovny.cz E-zdroje
- Klíčová slova
- Gliogenesis, Ion channel, Neonatal mouse, Neurogenesis, Patch-clamp technique, β-catenin signaling,
- MeSH
- beta-katenin genetika metabolismus MeSH
- imunohistochemie MeSH
- kultivované buňky MeSH
- membránové potenciály fyziologie MeSH
- metoda terčíkového zámku MeSH
- mezibuněčné signální peptidy a proteiny genetika metabolismus MeSH
- mozek cytologie metabolismus MeSH
- myši transgenní MeSH
- nervové kmenové buňky cytologie metabolismus MeSH
- neurogeneze fyziologie MeSH
- neuroglie cytologie metabolismus MeSH
- neurony cytologie metabolismus MeSH
- signální dráha Wnt fyziologie MeSH
- transkripční faktor 4 MeSH
- transkripční faktory BHLH-Zip genetika metabolismus MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- beta-katenin MeSH
- CTNNB1 protein, mouse MeSH Prohlížeč
- Dkk1 protein, mouse MeSH Prohlížeč
- mezibuněčné signální peptidy a proteiny MeSH
- Tcf4 protein, mouse MeSH Prohlížeč
- transkripční faktor 4 MeSH
- transkripční faktory BHLH-Zip 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.
Citace poskytuje Crossref.org
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