Transcriptional regulation of cortical neuron migration by POU domain factors

Science. 2002 Feb 22;295(5559):1528-32. doi: 10.1126/science.1067132.

Abstract

The identification of pathways mediated by the kinase Cdk5 and the ligand reelin has provided a conceptual framework for exploring the molecular mechanisms underlying proper lamination of the developing mammalian cerebral cortex. In this report, we identify a component of the regulation of Cdk5-mediated cortical lamination by genetic analysis of the roles of the class III POU domain transcription factors, Brn-1 and Brn-2, expressed during the development of the forebrain and coexpressed in most layer II-V cortical neurons. Brn-1 and Brn-2 appear to critically control the initiation of radial migration, redundantly regulating the cell-autonomous expression of the p35 and p39 regulatory subunits of Cdk5 in migrating cortical neurons, with Brn-1(-/-)/Brn-2(-/-) mice exhibiting cortical inversion.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Brain / cytology
  • Brain / embryology
  • Brain / metabolism
  • Cell Adhesion Molecules, Neuronal / genetics
  • Cell Adhesion Molecules, Neuronal / metabolism
  • Cell Line
  • Cell Movement
  • Cerebral Cortex / cytology
  • Cerebral Cortex / embryology
  • Cerebral Cortex / metabolism*
  • Cyclin-Dependent Kinase 5
  • Cyclin-Dependent Kinases / metabolism
  • Extracellular Matrix Proteins / genetics
  • Extracellular Matrix Proteins / metabolism
  • Female
  • Gene Targeting
  • Hippocampus / cytology
  • Hippocampus / embryology
  • Hippocampus / metabolism
  • Homeodomain Proteins
  • In Situ Hybridization
  • Male
  • Mice
  • Mutation
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Neurons / physiology*
  • Neuropeptides / genetics
  • Neuropeptides / physiology*
  • POU Domain Factors
  • Reelin Protein
  • Serine Endopeptidases
  • Trans-Activators / genetics
  • Trans-Activators / physiology*
  • Transcription Factors / genetics
  • Transcription Factors / physiology*
  • Transcription, Genetic*

Substances

  • Cdk5 activator p39
  • Cell Adhesion Molecules, Neuronal
  • Extracellular Matrix Proteins
  • Homeodomain Proteins
  • Nerve Tissue Proteins
  • Neuropeptides
  • POU Domain Factors
  • Reelin Protein
  • Trans-Activators
  • Transcription Factors
  • neuronal Cdk5 activator (p25-p35)
  • transcription factor Brn-2
  • Pou3f3 protein, mouse
  • Cyclin-Dependent Kinase 5
  • Cdk5 protein, mouse
  • Cyclin-Dependent Kinases
  • Reln protein, mouse
  • Serine Endopeptidases