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

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. (C) 2008 IBRO. Published by Elsevier Ltd. All rights reserved.