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

被引:71
作者
Hu, J. -G. [1 ,2 ,4 ]
Fu, S. -L. [4 ]
Wang, Y. -X. [4 ]
Li, Y. [4 ]
Jiang, X. -Y. [4 ]
Wang, X. -F. [4 ]
Qiu, M. -S. [3 ]
Lu, P. -H. [4 ]
Xu, X. -M. [1 ,2 ,3 ,4 ]
机构
[1] Indiana Univ, Sch Med, Stark Neurosci Res Inst, Spinal Cord & Brain Injury Res Grp, Indianapolis, IN 46202 USA
[2] Indiana Univ, Sch Med, Dept Neurol Surg, Indianapolis, IN 46202 USA
[3] Univ Louisville, Sch Med, Dept Anat Sci & Neurobiol, Louisville, KY 40292 USA
[4] Shanghai Jiao Tong Univ, Sch Med, Dept Neurobiol, Shanghai 200025, Peoples R China
关键词
differentiation; neural stem cells; oligodendrocytes; PDGF-AA; Erk1/2; Olig2;
D O I
10.1016/j.neuroscience.2007.10.050
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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.
引用
收藏
页码:138 / 147
页数:10
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