Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Astrocytes / cytology
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Astrocytes / physiology*
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Basic Helix-Loop-Helix Transcription Factors / genetics
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Basic Helix-Loop-Helix Transcription Factors / metabolism
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Cell Adhesion Molecules, Neuronal / genetics
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Cell Adhesion Molecules, Neuronal / metabolism
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Cell Culture Techniques
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Cell Differentiation / physiology*
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Cell Lineage
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Cells, Cultured
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Extracellular Matrix Proteins / genetics
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Extracellular Matrix Proteins / metabolism
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Intermediate Filament Proteins / genetics
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Intermediate Filament Proteins / metabolism
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Janus Kinases / genetics
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Janus Kinases / metabolism*
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Mice
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Mice, Knockout
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism*
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Nestin
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Neurons / cytology
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Neurons / physiology*
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RNA, Small Interfering / genetics
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RNA, Small Interfering / metabolism
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Reelin Protein
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STAT Transcription Factors / genetics
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STAT Transcription Factors / metabolism*
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Serine Endopeptidases / genetics
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Serine Endopeptidases / metabolism
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Stem Cells / cytology
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Stem Cells / physiology*
Substances
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Basic Helix-Loop-Helix Transcription Factors
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Cell Adhesion Molecules, Neuronal
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Dab1 protein, mouse
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Extracellular Matrix Proteins
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Intermediate Filament Proteins
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Nerve Tissue Proteins
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Nes protein, mouse
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Nestin
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RNA, Small Interfering
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Reelin Protein
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STAT Transcription Factors
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Neurogenic differentiation factor 1
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Janus Kinases
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Reln protein, mouse
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Serine Endopeptidases