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

Brain Res. 2015 Nov 2:1625:102-10. doi: 10.1016/j.brainres.2015.08.028. Epub 2015 Sep 1.

Abstract

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 ndufv2 is expressed in the developing cerebral cortex. In utero suppression of ndufv2 arrested neuronal migration, leading to accumulation of ectopic neurons in the intermediate zone. ndufv2 inhibition did not affect radial glia scaffold, progenitor cells or neurons survival. However, the loss of ndufv2 impairs neuronal multipolar-bipolar transition in vivo and polarization in vitro. Moreover, ndufv2 affected actin cytoskeleton and tubulin stabilization in cortical neurons. Overall, our findings establish a new NDUFV2 dependent mechanism underlying neuronal migration and psychiatric disorders.

Keywords: Developing cerebral cortex; In utero Electroporation; NDUFV2; Neuronal migration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Animals
  • Animals, Newborn
  • Caspase 3 / metabolism
  • Cell Movement / drug effects
  • Cell Movement / genetics*
  • Cell Survival / genetics
  • Cerebral Cortex* / cytology
  • Cerebral Cortex* / embryology
  • Cerebral Cortex* / growth & development
  • Electroporation
  • Embryo, Mammalian
  • Eye Proteins / metabolism
  • Gene Expression Regulation, Developmental / genetics*
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Homeodomain Proteins / metabolism
  • Mice
  • NADH Dehydrogenase / genetics
  • NADH Dehydrogenase / metabolism*
  • Neurons / physiology*
  • PAX6 Transcription Factor
  • Paired Box Transcription Factors / metabolism
  • RNA, Small Interfering / metabolism
  • Repressor Proteins / metabolism
  • Tubulin / metabolism

Substances

  • Actins
  • Eye Proteins
  • Homeodomain Proteins
  • PAX6 Transcription Factor
  • Paired Box Transcription Factors
  • Pax6 protein, mouse
  • RNA, Small Interfering
  • Repressor Proteins
  • Tubulin
  • Green Fluorescent Proteins
  • NADH Dehydrogenase
  • Caspase 3