NDUFV2 regulates neuronal migration in the developing cerebral cortex through modulation of the multipolar-bipolar transition

Abnormalities during brain development are tightly linked several psychiatric disorders. Mutations in NADH dehydrogenase ubiquinone flavoprotein 2 (NDUFV2) are responsible for schizophrenia, bipolar disorder and Parkinson's disease. However, the function of NDUFV2 during brain development remains unclear. Here we reported that ndufu2 is expressed in the developing cerebral cortex. In utero suppression of ndufu2 arrested neuronal migration, leading to accumulation of ectopic neurons in the intermediate zone. ndufu2 inhibition did not affect radial glia scaffold, progenitor cells or neurons survival. However, the loss of ndufu2 impairs neuronal multipolar-bipolar transition in vivo and polarization in vitro. Moreover, ndufu2 affected actin cytoskeleton and tubulin stabilization in cortical neurons. Overall, our findings establish a new NDUFV2 dependent mechanism underlying neuronal migration and psychiatric disorders. (C) 2015 Elsevier B.V. All rights reserved.