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

Identifikátory výsledku

  • 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>

Alternativní jazyky

  • 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.

Klasifikace

  • Druh

    J<sub>x</sub> - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

  • CEP obor

    ED - Fyziologie

  • OECD FORD obor

Návaznosti výsledku

  • 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

Ostatní

  • Rok uplatnění

    2016

  • Kód důvěrnosti údajů

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

Údaje specifické pro druh výsledku

  • 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