The interaction of Nogo-66 receptor with Nogo-p4 inhibits the neuronal differentiation of neural stem cells.

The Nogo-66 receptor (NgR) has been found throughout axons in the adult and maturing CNS. An interaction of Nogo on the oligodendrocyte surface with NgR on axons has been suggested to play an important role in limiting axonal growth. In our study, we found that neural stem cells (NSCs) derived from the spinal cords of rats expressed NgR significantly. After normal NSCs differentiation, the average neuronal neurite length was 97.80+/-6.97 microm and the percentage of differentiated neurons was 34.73+/-5.21% 3 days after the differentiation was initiated in vitro. If NSCs were allowed to differentiate in the presence of Nogo-p4 (the active segment of Nogo-66), the average neurite length and the percentage of differentiated neurons were decreased, respectively, to 60.31+/-6.58 microm and 10.26+/-1.22%. An siRNA-mediated knockdown of NgR on NSCs could reverse the inhibitory effect of Nogo-p4 and restore the average neuronal neurite length as well as the percentage of differentiated neurons to 94.01+/-8.37 microm and 31.84+/-4.03%. These results deepen our knowledge about the distribution of NgR and provide a possible strategy of treating NSCs to ameliorate neuronal differentiation after transplantation.