Angiopoietin-2 induces the neuronal differentiation of mouse embryonic NSCs via phosphatidylinositol 3 kinase-Akt pathway-mediated phosphorylation of mTOR.

The fate of neural stem cells (NSCs) is decided by numerous growth factors. Among these factors, the well-known angiogenic factor angiopoietin-2 (Ang-2) has been revealed to participate in neurogenesis separate from its role in angiogenesis. However, the effect of Ang-2 on the fate determination of mouse embryonic NSCs and the underlying mechanism remain unclear. This result of this study indicated that treatment of mouse embryonic NSCs with 200 ng/ml Ang-2 significantly promoted neuronal differentiation without affecting glial differentiation, and mammalian target of rapamycin (mTOR) was phosphorylated in a phosphatidylinositol 3-kinase (PI3K)/Akt-dependent manner during this process. Rapamycin, a specific mTOR inhibitor, suppressed the increase in neuronal differentiation stimulated by Ang-2, and this suppression did not result from an effect of Ang-2 or rapamycin on the apoptosis of differentiated NSCs. Collectively, our research demonstrates that PI3K/Akt pathway-mediated mTOR phosphorylation plays an important role in the Ang-2-enhanced neuronal differentiation of mouse embryonic NSCs.