GSK3β, But Not GSK3α, Inhibits the Neuronal Differentiation of Neural Progenitor Cells As a Downstream Target of Mammalian Target of Rapamycin Complex1
| Autor: | Keejung Yoon, Sun-Young Kim, Jyhyun Ahn, J.M. Lee, Junghun Lee, Jinyong Choi, Jiwon Jang, Seo-Ho Oh |
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| Rok vydání: | 2014 |
| Předmět: |
Indoles
Cellular differentiation mTORC1 Mechanistic Target of Rapamycin Complex 1 Biology Cell Line Maleimides Glycogen Synthase Kinase 3 Mice Original Research Reports Neural Stem Cells Tubulin Animals Humans Progenitor cell Kinase activity GSK3B Glycogen Synthase Kinase 3 beta TOR Serine-Threonine Kinases Neurogenesis Cell Differentiation Cell Biology Hematology Neural stem cell Cell biology Multiprotein Complexes Signal transduction Signal Transduction Developmental Biology |
| Zdroj: | Stem Cells and Development. 23:1121-1133 |
| ISSN: | 1557-8534 1547-3287 |
| DOI: | 10.1089/scd.2013.0397 |
| Popis: | Glycogen synthase kinase 3 (GSK3) acts as an important regulator during the proliferation and differentiation of neural progenitor cells (NPCs), but the roles of the isoforms of this molecule (GSK3α and GSK3β) have not been clearly defined. In this study, we investigated the functions of GSK3α and GSK3β in the context of neuronal differentiation of murine NPCs. Treatment of primary NPCs with a GSK3 inhibitor (SB216763) resulted in an increase in the percentage of TuJ1-positive immature neurons, suggesting an inhibitory role of GSK3 in embryonic neurogenesis. Downregulation of GSK3β expression increased the percentage of TuJ1-positive cells, while knock-down of GSK3α seemed to have no effect. When primary NPCs were engineered to stably express either isoform of GSK3 using retroviral vectors, GSK3β, but not GSK3α, inhibited neuronal differentiation and helped the cells to maintain the characteristics of NPCs. Mutant GSK3β (Y216F) failed to suppress neuronal differentiation, indicating that the kinase activity of GSK3β is important for this regulatory function. Similar results were obtained in vivo when a retroviral vector expressing GSK3β was delivered to E9.5 mouse brains using the ultrasound image-guided gene delivery technique. In addition, SB216763 was found to block the rapamycin-mediated inhibition of neuronal differentiation of NPCs. Taken together, our results demonstrate that GSK3β, but not GSK3α, negatively controls the neuronal differentiation of progenitor cells and that GSK3β may act downstream of the mammalian target of rapamycin complex1 signaling pathway. |
| Databáze: | OpenAIRE |
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