Reelin, Rap1 and N-cadherin orient the migration of multipolar neurons in the developing neocortex

Nat Neurosci. 2011 Jun;14(6):697-703. doi: 10.1038/nn.2816. Epub 2011 Apr 24.

Abstract

Projection neurons migrate from the ventricular zone to the neocortical plate during the development of the mouse brain. Their overall movement is radial, but they become multipolar and move nonradially in the intermediate zone. Here we show that Reelin, the Rap1 GTPase and N-cadherin (NCad) are important for multipolar neurons to polarize their migration toward the cortical plate. Inhibition and rescue experiments indicated that Reelin regulates migration through Rap1 and Akt, and that the Rap1-regulated GTPases RalA, RalB, Rac1 and Cdc42 are also involved. We found that Rap1 regulated the plasma membrane localization of NCad and NCad rescued radial polarization when Rap1 was inhibited. However, inhibition of Rap1 or NCad had little effect on glia-dependent locomotion. We propose a multistep mechanism in which Reelin activates Rap1, Rap1 upregulates NCad, and NCad is needed to orient cell migration.

Publication types

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

MeSH terms

  • Animals
  • Cadherins / metabolism*
  • Cell Adhesion Molecules, Neuronal / metabolism*
  • Cell Differentiation / physiology*
  • Cell Movement / physiology*
  • Extracellular Matrix Proteins / metabolism*
  • Mice
  • Mice, Inbred Strains
  • Neocortex / cytology*
  • Neocortex / embryology*
  • Nerve Tissue Proteins / metabolism*
  • Neurons / metabolism*
  • Neurons / physiology
  • Serine Endopeptidases / metabolism*
  • rap1 GTP-Binding Proteins / metabolism*

Substances

  • Cadherins
  • Cell Adhesion Molecules, Neuronal
  • Extracellular Matrix Proteins
  • Nerve Tissue Proteins
  • Serine Endopeptidases
  • reelin protein
  • rap1 GTP-Binding Proteins