Reelin and cofilin cooperate during the migration of cortical neurons: a quantitative morphological analysis

Development. 2016 Mar 15;143(6):1029-40. doi: 10.1242/dev.134163. Epub 2016 Feb 18.

Abstract

In reeler mutant mice, which are deficient in reelin (Reln), the lamination of the cerebral cortex is disrupted. Reelin signaling induces phosphorylation of LIM kinase 1, which phosphorylates the actin-depolymerizing protein cofilin in migrating neurons. Conditional cofilin mutants show neuronal migration defects. Thus, both reelin and cofilin are indispensable during cortical development. To analyze the effects of cofilin phosphorylation on neuronal migration we used in utero electroporation to transfect E14.5 wild-type cortical neurons with pCAG-EGFP plasmids encoding either a nonphosphorylatable form of cofilin 1 (cofilin(S3A)), a pseudophosphorylated form (cofilin(S3E)) or wild-type cofilin 1 (cofilin(WT)). Wild-type controls and reeler neurons were transfected with pCAG-EGFP. Real-time microscopy and histological analyses revealed that overexpression of cofilin(WT) and both phosphomutants induced migration defects and morphological abnormalities of cortical neurons. Of note, reeler neurons and cofilin(S3A)- and cofilin(S3E)-transfected neurons showed aberrant backward migration towards the ventricular zone. Overexpression of cofilin(S3E), the pseudophosphorylated form, partially rescued the migration defect of reeler neurons, as did overexpression of Limk1. Collectively, the results indicate that reelin and cofilin cooperate in controlling cytoskeletal dynamics during neuronal migration.

Keywords: Actin cytoskeleton; Cofilin phosphorylation; In utero electroporation; Neuronal migration; Reelin signaling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Adhesion Molecules, Neuronal / metabolism*
  • Cell Count
  • Cell Movement*
  • Cell Shape*
  • Cerebral Cortex / cytology*
  • Cofilin 1 / metabolism*
  • Electroporation
  • Embryo, Mammalian / cytology
  • Extracellular Matrix Proteins / metabolism*
  • Female
  • Mice, Inbred C57BL
  • Nerve Tissue Proteins / metabolism*
  • Neurons / cytology*
  • Neurons / metabolism
  • Serine Endopeptidases / metabolism*
  • Transfection

Substances

  • Cell Adhesion Molecules, Neuronal
  • Cofilin 1
  • Extracellular Matrix Proteins
  • Nerve Tissue Proteins
  • Serine Endopeptidases
  • reelin protein