Connexin 43 controls the multipolar phase of neuronal migration to the cerebral cortex

Proc Natl Acad Sci U S A. 2012 May 22;109(21):8280-5. doi: 10.1073/pnas.1205880109. Epub 2012 May 7.

Abstract

The prospective pyramidal neurons, migrating from the proliferative ventricular zone to the overlaying cortical plate, assume multipolar morphology while passing through the transient subventricular zone. Here, we show that this morphogenetic transformation, from the bipolar to the mutipolar and then back to bipolar again, is associated with expression of connexin 43 (Cx43) and, that knockdown of Cx43 retards, whereas its overexpression enhances, this morphogenetic process. In addition, we have observed that knockdown of Cx43 reduces expression of p27, whereas overexpression of p27 rescues the effect of Cx43 knockdown in the multipolar neurons. Furthermore, functional gap junction/hemichannel domain, and the C-terminal domain of Cx43, independently enhance the expression of p27 and promote the morphological transformation and migration of the multipolar neurons in the SVZ/IZ. Collectively, these results indicate that Cx43 regulates the passage of migrating neurons through their multipolar stage via p27 signaling and that interference with this process, by either genetic and/or environmental factors, may cause cortical malformations.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism
  • Cell Membrane / physiology
  • Cell Movement / physiology*
  • Cerebral Cortex* / cytology
  • Cerebral Cortex* / embryology
  • Cerebral Cortex* / physiology
  • Connexin 43 / chemistry
  • Connexin 43 / genetics
  • Connexin 43 / physiology*
  • Cyclin-Dependent Kinase Inhibitor p27 / genetics
  • Cyclin-Dependent Kinase Inhibitor p27 / physiology*
  • Female
  • Gap Junctions / physiology
  • Gene Knockdown Techniques
  • Ion Channels / physiology
  • Mice
  • Mice, Inbred Strains
  • Pregnancy
  • Protein Structure, Tertiary
  • Pyramidal Cells / cytology*
  • Pyramidal Cells / physiology

Substances

  • Cdkn1b protein, mouse
  • Connexin 43
  • GJA1 protein, mouse
  • Ion Channels
  • Cyclin-Dependent Kinase Inhibitor p27
  • Calcium