Abstract
Platelet-derived growth factor-AA (PDGF-AA) has been used as a potent mitogen for the proliferation of oligodendrocyte progenitor cells (OPCs). Whether it plays a role in oligodendrocyte lineage differentiation of neural stem cells (NSCs) is unclear. Here we report that PDGF-AA is an instructional signal required for the differentiation of embryonic forebrain NSCs into O4-positive oligodendrocytes. Moreover, such PDGF-AA-induced oligodendrocyte differentiation appears to be mediated by the extracellular signal-regulated kinases 1 and 2 (Erk1/2) but not phosphatidylinositol-3 kinase (PI3K) pathway. Finally, PDGF-AA treatment resulted in a significant increase in the expression of the oligodendrocyte-specific transcriptional factor Olig2 in an Erk1/2-dependent mechanism at early stages of oligodendrogliogenesis. Together, our studies provide cellular and molecular evidence to suggest that PDGF-AA is a key molecule that regulates the differentiation of embryonic NSCs into oligodendrocytes. The action of PDGF-AA is mediated by the activation of Erk pathway which involves the downstream upregulation of transcriptional factor Olig2.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Basic Helix-Loop-Helix Transcription Factors / genetics
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Basic Helix-Loop-Helix Transcription Factors / physiology
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Blotting, Western
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Cell Differentiation / physiology*
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Cell Lineage / physiology*
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Cells, Cultured
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Extracellular Signal-Regulated MAP Kinases / physiology*
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Female
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Glial Fibrillary Acidic Protein / physiology
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Immunohistochemistry
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In Situ Nick-End Labeling
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / physiology
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Neurons / physiology
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Oligodendrocyte Transcription Factor 2
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Oligodendroglia / physiology*
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Phosphatidylinositol 3-Kinases / physiology
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Platelet-Derived Growth Factor / physiology*
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Pregnancy
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Rats
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Rats, Wistar
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Signal Transduction / physiology*
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Stem Cells / metabolism
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Tubulin / physiology
Substances
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Basic Helix-Loop-Helix Transcription Factors
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Glial Fibrillary Acidic Protein
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Nerve Tissue Proteins
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Olig2 protein, rat
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Oligodendrocyte Transcription Factor 2
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Platelet-Derived Growth Factor
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Tubulin
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platelet-derived growth factor A
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Phosphatidylinositol 3-Kinases
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Extracellular Signal-Regulated MAP Kinases