Neuronal position in the developing brain is regulated by mouse disabled-1

Nature. 1997 Oct 16;389(6652):733-7. doi: 10.1038/39607.

Abstract

During mammalian brain development, immature neurons migrate radially from the neuroectoderm to defined locations, giving rise to characteristic cell layers. Here we show that targeted disruption of the mouse disabled1 (mdab1) gene disturbs neuronal layering in the cerebral cortex, hippocampus and cerebellum. The gene encodes a cytoplasmic protein, mDab1 p80, which is expressed and tyrosine-phosphorylated in the developing nervous system. It is likely to be an adaptor protein, docking to others through its phosphotyrosine residues and protein-interacting domain. The mdab1 mutant phenotype is very similar to that of the reeler mouse. The product of the reeler gene, Reelin, is a secreted protein that has been proposed to act as an extracellular signpost for migrating neurons. Because mDab1 is expressed in wild-type cortical neurons, and Reelin expression is normal in mdab1 mutants, mDab1 may be part of a Reelin-regulated or parallel pathway that controls the final positioning of neurons.

Publication types

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

MeSH terms

  • Animals
  • Brain / abnormalities
  • Brain / cytology
  • Brain / embryology*
  • Cell Adhesion Molecules, Neuronal / genetics
  • Cell Adhesion Molecules, Neuronal / physiology
  • Cell Line
  • Cell Movement
  • Cerebellum / abnormalities
  • Cerebellum / embryology
  • Extracellular Matrix Proteins / genetics
  • Extracellular Matrix Proteins / physiology
  • Gene Targeting
  • Mice
  • Mice, Neurologic Mutants
  • Mutagenesis
  • Neocortex / abnormalities
  • Neocortex / embryology
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / physiology*
  • Neurons / physiology*
  • Serine Endopeptidases
  • Signal Transduction

Substances

  • Cell Adhesion Molecules, Neuronal
  • Dab1 protein, mouse
  • Extracellular Matrix Proteins
  • Nerve Tissue Proteins
  • Serine Endopeptidases
  • reelin protein