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

Abstract

In reeler mutant mice deficient in Reelin 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 for a nonphosphorylatable form of cofilin (cofilinS3A), a pseudophosphorylated form (cofilinS3E) or wild-type cofilin (cofilinwt). Wild-type controls and reeler neurons were transfected with pCAG-EGFP. Real-time microscopy and histological analyses revealed that overexpression of each, cofilinwt, cofilinS3A, and cofilinS3E, induced migration defects and morphological abnormalities of cortical neurons. Of note, reeler neurons, cofilinS3A- and cofilinS3E-transfected neurons showed aberrant backward migration towards the ventricular zone. Overexpression of cofilinS3E, the pseudophosphorylated form, partially rescued the migration defect of reeler neurons as did overexpression of LIM kinase1. Collectively, the results indicate that Reelin and cofilin cooperate in controlling cytoskeletal dynamics during neuronal migration.