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

Kód výsledku v 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>

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

ED - Fyziologie

OECD FORD obor

—

Projekt

<a href="/cs/project/GBP304%2F12%2FG069" target="_blank" >GBP304/12/G069: Projekt excelence v oblasti neurověd</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2016

Kód důvěrnosti údajů

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

Název periodika

Brain research

ISSN

1872-6240

e-ISSN

—

Svazek periodika

1641

Číslo periodika v rámci svazku

nov.

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

15

Strana od-do

73-87

Kód UT WoS článku

000387527100009

EID výsledku v databázi Scopus

2-s2.0-84988905741