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.

[This corrects the article on p. 1895 in vol. 11, PMID: 30972213.].

Objective To observe the effects of PTEN silencing on axon regeneration and functional recovery after spinal cord injury (SCI).Methods Four groups were designed:DMEM、lenti-control、lenti-scramble、lenti-shRNA.Cortical neurons were seeded on or adjacent to chondroitin sulfate proteoglycans (CSPGs).Three days after lentivirus infection,the expression of PTEN were assessed by Western blot,and immunocytochemistry method were applied to examine the length,number and crossing behavior of neurites;Lentivirus was locally injected into the conical motor area of the rats with spinal cord injury.1 week later,the expression of PTEN was assessed by Western blot.6 weeks later,motor function of hind limbs was evaluated by Basso Beattie Bresnahan (BBB) score,while the expressions of green fluorescence in injured spinal cord were observed by fluorescence microscope,and immunohistochemical method was used to observe the expression of synaptophysin changes in spinal tissues.Results Less expression of PTEN was detected in lentivirus-shRNA,and neurites with PTEN silencing exhibited significant enhancements in elongation,initiation and crossing ability when they encountered CSPGs in vitro.Better hindlimb functional recovery,less expression of PTEN and more synaptophysin positive response area were detected in rats injected with lentivirus-shRNA compared with other groups.Moreover,green fluorescence was found in the caudal region of injured spinal cord of rats injected with lentivirusshRNA.Conclusion Lentiviral-mediated PTEN-shRNA can significantly improve the axon regeneration and neurological functional recovery after spinal cord injury.