Switching on mTORC1 induces neurogenesis but not proliferation in neural stem cells of young mice.

Abstract Recent evidence reported that activation of the mechanistic target of rapamycin complex 1 (mTORC1) induces terminal differentiation of neural stem cells (NSCs) in the neonatal subventricular zone (SVZ), but did not affect their proliferation. Here, we investigated whether such an effect of hyperactive mTORC1 would be recapitulated in young adults following removal of the negative mTORC1 regulator TSC1 as seen in the neurological disorder tuberous sclerosis complex, TSC. Conditional mTORC1 activation in NSCs of 3–4 weeks old mice resulted in the generation of proliferative (Ki67 + ) cells and newborn neuroblasts. However, hyperactive mTORC1 did not induce NSCs to proliferate, consistent with the findings that mTORC1 induces symmetric division and differentiation of slow-cycling NSCs into proliferative daughter cells. Taken together these data suggest that hyperactivity of mTORC1 could lead to the progressive loss of NSCs over time.