Cdk5 phosphorylation of ErbB4 is required for tangential migration of cortical interneurons

Cereb Cortex. 2015 Apr;25(4):991-1003. doi: 10.1093/cercor/bht290. Epub 2013 Oct 18.

Abstract

Interneuron dysfunction in humans is often associated with neurological and psychiatric disorders, such as epilepsy, schizophrenia, and autism. Some of these disorders are believed to emerge during brain formation, at the time of interneuron specification, migration, and synapse formation. Here, using a mouse model and a host of histological and molecular biological techniques, we report that the signaling molecule cyclin-dependent kinase 5 (Cdk5), and its activator p35, control the tangential migration of interneurons toward and within the cerebral cortex by modulating the critical neurodevelopmental signaling pathway, ErbB4/phosphatidylinositol 3-kinase, that has been repeatedly linked to schizophrenia. This finding identifies Cdk5 as a crucial signaling factor in cortical interneuron development in mammals.

Keywords: cerebral cortex; interneurons; migration; mouse; phosphorylation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • COS Cells
  • Cell Movement / physiology*
  • Cerebral Cortex / embryology
  • Cerebral Cortex / physiology*
  • Cyclin-Dependent Kinase 5 / genetics
  • Cyclin-Dependent Kinase 5 / metabolism*
  • GABAergic Neurons / physiology
  • Glutamate Decarboxylase / genetics
  • Glutamate Decarboxylase / metabolism
  • Interneurons / physiology*
  • Keratins / metabolism
  • Mice, Transgenic
  • Phosphatidylinositol 3-Kinase / metabolism
  • Phosphorylation
  • Phosphotransferases / genetics
  • Phosphotransferases / metabolism
  • Receptor, ErbB-4 / genetics
  • Receptor, ErbB-4 / metabolism*
  • Signal Transduction

Substances

  • Cdk5r1 protein, mouse
  • Keratins
  • Phosphotransferases
  • Phosphatidylinositol 3-Kinase
  • Erbb4 protein, mouse
  • Receptor, ErbB-4
  • Cyclin-Dependent Kinase 5
  • Cdk5 protein, mouse
  • Glutamate Decarboxylase
  • glutamate decarboxylase 1