Nuclear distribution element 1 is involved in cell proliferation in the ventricular-subventricular zone during early...

The ventricular-subventricular zone (V-SVZ) is a specialized neurogenic niche localized on the walls of the lateral ventricles in the postnatal mammalian brain. In the V-SVZ, neural stem cells (NSCs) generate transit-amplifying neural progenitor cells, which produce neuroblasts. V-SVZ-derived neuroblasts have proliferative potential and migrate through the rostral migratory stream (RMS) toward the olfactory bulb (OB), where they differentiate into OB interneurons. However, the manner in which V-SVZ cell proliferation and OB neurogenesis are regulated during early postnatal brain development, a transition period from embryonic to adult stage, remains unclear. We focused on the role of the dynein cofactor nuclear distribution element 1 (NDE1) in early postnatal brain development. We found that Nde1 mRNA is expressed in NSCs, transit-amplifying neural progenitor cells, and neuroblasts in the V-SVZ in mice at early postnatal stage, and this expression was detected in migrating neuroblasts in the RMS and OB. Nde1 knockdown via the in vivo postnatal electroporation of Nde1 short hairpin RNA (shRNA) in a neonatal mouse brain decreased V-SVZ cell proliferation, which was rescued by overexpression of wild-type NDE1-shRNA resistant but not by overexpression of dynein-binding region-deficient NDE1-shRNA resistant. The V-SVZ cell proliferation defect was followed by impaired proliferation of V-SVZ-derived neuroblasts, thus leading to decreased generation of neuroblasts, which resulted in the reduction of newly generated OB neurons. Therefore, these results indicate that NDE1 is involved in the proliferation of NSCs and neural progenitors in the developing V-SVZ, suggesting that NDE1 plays an important role in early postnatal V-SVZ-derived neurogenesis.