PDGF-AA instructs embryonic neural stem cells to differentiate into the oligodendrocyte lineage through the activation of Erk but not PI3K signaling pathway

【作者】 胡建国； 富赛里； 李莹； 王艳霞； 蒋晓燕； 金建强； 陆佩华； 徐晓明；

【机构】 上海第二医科大学神经生物学实验室；

【摘要】 <正>Platelet-derived growth factor-AA (PDGF-AA) has been used as a potent mitogen for the proliferation of oligodendrocyte precursor cells (OPCs). When combined with bFGF, it causes a sustained self-renewal of the OPCs and prohibits them from differentiating into oligodendrocytes. The PDGF-AA-contained B104CM can act as an instructive signal to induce neural stem cells (NSCs) to commit to the oligodendrocyte lineage. These findings raise the possibility that PDGF-AA may play a key role in oligodendrocyte differentiation from the NSCs. Here we report that PDGF-AA is an instructional signal required for the differentiation of embryonic forebrain NSCs into oligodendrocytes. Remarkably, such PDGF-AA-induced oligodendrocyte differentiation appears to be mediated by the Erk, but not PI3K, signal pathway. Moreover, two transcription factors c-fos and c-jun are involved in the Erk-mediated oligodendrocyte differentiation. Finally, Olig2, a transcriptional factor essential for oligodendrogliogenesis, is upregulated in the PDGF-AA-induced oligodendrocyte differentiation. Taken together, these results provide strong cellular and molecular evidence to suggest that PDGF-AA is a key molecule that regulates the differentiation of oligodendrocytes from embryonic NSCs. The action of PDGF-AA is mediated by the activation of Erk signaling pathway with sequential upregulation of the transcriptional factors c-fos, c-jun and Olig2.更多还原