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.
Hu
J-G
JG
Department of Neurobiology, Shanghai Jiaotong University School of Medicine, Shanghai 200025, People's Republic of China.
Fu
S-L
SL
Wang
Y-X
YX
Li
Y
Y
Jiang
X-Y
XY
Wang
X-F
XF
Qiu
M-S
MS
Lu
P-H
PH
Xu
X-M
XM
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000502:physiology; D015153:Blotting, Western; D002454:Cell Differentiation / Q000502:physiology*; D019070:Cell Lineage / Q000502:physiology*; D002478:Cells, Cultured; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology*; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000502:physiology; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology; D009474:Neurons / Q000502:physiology; D000076104:Oligodendrocyte Transcription Factor 2; D009836:Oligodendroglia / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D010982:Platelet-Derived Growth Factor / Q000502:physiology*; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000502:physiology*; D013234:Stem Cells / Q000378:metabolism; D014404:Tubulin / Q000502:physiology
D051792:Basic Helix-Loop-Helix Proteins; D048049:Extracellular Signal-Regulated MAP Kinases; D005904:Glial Fibrillary Acidic Protein; D009419:Nerve Tissue Proteins; D000076104:Oligodendrocyte Transcription Factor 2; D019869:Phosphatidylinositol 3-Kinases; D010982:Platelet-Derived Growth Factor; D014404:Tubulin; C522729:Olig2 protein, rat; C075278:platelet-derived growth factor A