Expression of Disabled 1 suppresses astroglial differentiation in neural stem cells
| Autor: | Min-Ji Kim, Il-Sun Kwon, Sung-Kuk Cho, Haeyoung Suh-Kim, Noriaki Mitsuda, Ming Jer Tsai, Young-Don Lee |
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| Rok vydání: | 2009 |
| Předmět: |
Yotari
Cell Adhesion Molecules Neuronal Cellular differentiation Cell Culture Techniques Nerve Tissue Proteins Biology Article Nestin Mice Cellular and Molecular Neuroscience Astrocyte differentiation Intermediate Filament Proteins Neurosphere Basic Helix-Loop-Helix Transcription Factors Animals Cell Lineage RNA Small Interfering Molecular Biology Cells Cultured Janus Kinases Mice Knockout Neurons NeuroD Extracellular Matrix Proteins Stem Cells Serine Endopeptidases Neurogenesis Cell Differentiation Cell Biology DAB1 Neural stem cell Reelin Protein STAT Transcription Factors nervous system Astrocytes Neuroscience |
| Zdroj: | Molecular and Cellular Neuroscience. 40:50-61 |
| ISSN: | 1044-7431 |
| DOI: | 10.1016/j.mcn.2008.08.012 |
| Popis: | Disabled 1 (Dab1), a cytoplasmic adaptor protein expressed predominantly in the CNS, transduces a Reelin-initiated signaling that controls neuronal migration and positioning during brain development. To determine the role of Dab1 in neural stem cell (NSC) differentiation, we established a culture of neurospheres derived from the embryonic forebrain of the Dab1(-/-) mice, yotari. Differentiating Dab1(-/-) neurospheres exhibited a higher expression of GFAP, an astrocytic marker, at the expense of neuronal markers. Under Dab1-deficient condition, the expression of NeuroD, a transcription factor for neuronal differentiation, was decreased and the JAK-STAT pathway was evidently increased during differentiation of NSC, suggesting the possible involvement of Dab1 in astrocyte differentiation via JAK-STAT pathway. Notably, expression of neural and glial markers and the level of JAK-STAT signaling molecules were not changed in differentiating NSC by Reelin treatment, indicating that differentiation of NSC is Reelin-independent. Immunohistochemical analyses showed a decrease in the number of neurons and an increase in the number of GFAP-positive cells in developing yotari brains. Our results suggest that Dab1 participates in the differentiation of NSCs into a specific cell lineage, thereby maintaining a balance between neurogenesis and gliogenesis. |
| Databáze: | OpenAIRE |
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