Manipulating Wnt signaling at different subcellular levels affects the fate of neonatal neural stem/progenitor cells

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378041%3A_____%2F16%3A00468303" target="_blank" >RIV/68378041:_____/16:00468303 - isvavai.cz</a>

Result on the web

<a href="http://dx.doi.org/10.1016/j.brainres.2016.09.026" target="_blank" >http://dx.doi.org/10.1016/j.brainres.2016.09.026</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.brainres.2016.09.026" target="_blank" >10.1016/j.brainres.2016.09.026</a>

Result language

angličtina

Original language name

Manipulating Wnt signaling at different subcellular levels affects the fate of neonatal neural stem/progenitor cells

Original language description

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/beta-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 beta-catenin protein and Wnt/beta-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 hyper-activation 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 beta-catenin-dependent signaling in neural progenitors in the neonatal brain.

Czech name

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Czech description

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Type

J_x - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

CEP classification

ED - Physiology

OECD FORD branch

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Project

<a href="/en/project/GBP304%2F12%2FG069" target="_blank" >GBP304/12/G069: Project of excellence in the field of neuroscience</a><br>

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2016

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Brain research

ISSN

1872-6240

e-ISSN

—

Volume of the periodical

1641

Issue of the periodical within the volume

nov.

Country of publishing house

NL - THE KINGDOM OF THE NETHERLANDS

Number of pages

15

Pages from-to

73-87

UT code for WoS article

000387527100009

EID of the result in the Scopus database

2-s2.0-84988905741