Inhibition of canonical Wnt signaling promotes gliogenesis in P0-NSCs.

KUNKE, David, Vítězslav BRYJA, Line MYGLAND, Ernest ARENAS and Stefan KRAUSS. Inhibition of canonical Wnt signaling promotes gliogenesis in P0-NSCs. Biochemical and Biophysical Research Communications. 2009, vol. 386, No 4, 6 pp. ISSN 0006-291X.

Basic information

• Original name: Inhibition of canonical Wnt signaling promotes gliogenesis in P0-NSCs.
• Name in Czech: Inhibice kanonické Wnt signalizace podporuje gliogenesi v PO-NSC
• Authors: KUNKE, David (203 Czech Republic, guarantor), Vítězslav BRYJA (203 Czech Republic), Line MYGLAND (752 Sweden), Ernest ARENAS (724 Spain) and Stefan KRAUSS (578 Norway).
• Edition: Biochemical and Biophysical Research Communications, 2009, 0006-291X.

Other information

• Original language: English
• Type of outcome: Article in a journal
• Field of Study: Genetics and molecular biology
• Country of publisher: United States of America
• Confidentiality degree: is not subject to a state or trade secret
• Impact factor: Impact factor: 2.548
• RIV identification code: RIV/00216224:14310/09:00036973
• Organization unit: Faculty of Science
• UT WoS: 000268462100016
• Keywords (in Czech): diferenciace, gliogeneze, neuronalni progenitorove bunky, kanonicke Wnt- signalovani, rozpustny Frizzled protein
• Keywords in English: Differentiation; Gliogenesis; Neuronal progenitor cells; Canonical Wnt signaling; Soluble Frizzled related protein

Abstract

Wnt signaling plays an essential role in the development of mammalian central nervous system. We investigated the impact of activation/inhibition of the Wnt signaling pathway on neuronal/glial differentiation in neurospheres derived from neonatal mouse forebrains. For short term alterations, neurospheres were stimulated with recombinant Wnt-3a, Wnt-5a and the Wnt inhibitor Dickkopf-1 (Dkk1). Furthermore, neurospheres were transduced with retroviral vectors encoding Wnt-3a, Wnt-7a and their inhibitors Dkk1 and soluble Frizzled related protein-5 (sFRP5). Long-term activation of Wnt pathway by Wnt-7a or by treatment with GSK3 inhibitors promoted a moderate increase of the neuronal differentiation and blocked gliogenesis. In contrast, Wnt pathway inhibition in neurospheres, induced by retroviral overexpression of either Dkk1 or sFRP5, robustly increased the gliogenesis at the expense of neurogenesis. In summary, our data demonstrate that activation or inhibition of Wnt/beta-catenin signaling in neurospheres regulates neuronal and glial differentiation, respectively. Thus, our results suggest that Wnt signaling may also contribute to regulate these processes in the neonatal brain.

Abstract (in Czech)

Signální dráha Wnt má klíčovou roli ve vývoji centrálního nervového systému. V této studii jsou sledovali, jaké jsou důsledky aktivace/inhibice Wnt signalizace na neurální a gliální diferenciaci v neurosférach z telencefalu novorozených myší. Ukazujeme že overexprese Wnt inhibitorů (Dkk1 a sFRP5) podporuje gliální diferenciaci, zatímco overexprese Wnt ligandu (Wnt7a) nebo farmakologická aktivace Wnt dráhy pomoci inhibitorů GSK3beta napomáhá diferenciaci neurální. Tyto výsledky ukazují, že aktivita Wnt dráhy určuje, kterým směrem budou neurální prekurzory diferencovat.

Links

• MSM0021622430, plan (intention): Name: Funkční a molekulární charakteristiky nádorových a normálních kmenových buněk - identifikace cílů pro nová terapeutika a terapeutické strategie

Investor: Ministry of Education, Youth and Sports of the CR, Functional and molecular characteristics of cancer and normal stem cells - identification of targets for novel therapeutics and therapeutic strategies