Platelet-derived growth factor-AA mediates oligodendrocyte lineage differentiation through activation of extracellular signal-regulated kinase signaling pathway

Neuroscience. 2008 Jan 2;151(1):138-47. doi: 10.1016/j.neuroscience.2007.10.050. Epub 2007 Nov 17.


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

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / physiology
  • Blotting, Western
  • Cell Differentiation / physiology*
  • Cell Lineage / physiology*
  • Cells, Cultured
  • Extracellular Signal-Regulated MAP Kinases / physiology*
  • Female
  • Glial Fibrillary Acidic Protein / physiology
  • Immunohistochemistry
  • In Situ Nick-End Labeling
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / physiology
  • Neurons / physiology
  • Oligodendrocyte Transcription Factor 2
  • Oligodendroglia / physiology*
  • Phosphatidylinositol 3-Kinases / physiology
  • Platelet-Derived Growth Factor / physiology*
  • Pregnancy
  • Rats
  • Rats, Wistar
  • Signal Transduction / physiology*
  • Stem Cells / metabolism
  • Tubulin / physiology


  • Basic Helix-Loop-Helix Transcription Factors
  • Glial Fibrillary Acidic Protein
  • Nerve Tissue Proteins
  • Olig2 protein, rat
  • Oligodendrocyte Transcription Factor 2
  • Platelet-Derived Growth Factor
  • Tubulin
  • platelet-derived growth factor A
  • Phosphatidylinositol 3-Kinases
  • Extracellular Signal-Regulated MAP Kinases