title: Reelin and cofilin cooperate during the migration of cortical neurons: a quantitative morphological analysis.
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.
authors.affiliation: Institute for Structural Neurobiology, Center for Molecular Neurobiology Hamburg (ZMNH), University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany.
authors.forename: Xuejun
authors.initials: X
authors.lastname: Chai
authors.affiliation: Institute for Structural Neurobiology, Center for Molecular Neurobiology Hamburg (ZMNH), University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany College of Veterinary Medicine, Northwest A&F University, 712100 Yangling, People's Republic of China.
authors.forename: Shanting
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Institute of Zoology, School of Life Science, Lanzhou University, 730000 Lanzhou, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Fan
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, 712100 Yangling, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, 712100 Yangling, People's Republic of China.
authors.forename: Xi
authors.initials: X
authors.lastname: Lu
authors.affiliation: Institute of Zoology, School of Life Science, Lanzhou University, 730000 Lanzhou, People's Republic of China.
authors.forename: Hong
authors.initials: H
authors.lastname: Shao
authors.affiliation: Institute for Structural Neurobiology, Center for Molecular Neurobiology Hamburg (ZMNH), University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany.
authors.forename: Shaobo
authors.initials: S
authors.lastname: Wang
authors.affiliation: Institute for Structural Neurobiology, Center for Molecular Neurobiology Hamburg (ZMNH), University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany.
authors.forename: Lingzhen
authors.initials: L
authors.lastname: Song
authors.affiliation: UKE Microscopy Imaging Facility (UMIF), University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany.
authors.forename: Antonio Virgilio
authors.initials: AV
authors.lastname: Failla
authors.affiliation: UKE Microscopy Imaging Facility (UMIF), University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Zobiak
authors.affiliation: Institute of Anatomy and Molecular Embryology, Ruhr University Bochum, 44780 Bochum, Germany.
authors.forename: Hans G
authors.initials: HG
authors.lastname: Mannherz
authors.affiliation: Institute for Structural Neurobiology, Center for Molecular Neurobiology Hamburg (ZMNH), University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany michael.frotscher@zmnh.uni-hamburg.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Frotscher
mesh_terms: D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism*; D002452:Cell Count; D002465:Cell Movement; D048430:Cell Shape; D002540:Cerebral Cortex / Q000166:cytology*; D051338:Cofilin 1 / Q000378:metabolism*; D018274:Electroporation; D004622:Embryo, Mammalian / Q000166:cytology; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005260:Female; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D000091042:Reelin Protein; D012697:Serine Endopeptidases / Q000378:metabolism*; D014162:Transfection
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D051338:Cofilin 1; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D000091042:Reelin Protein; C000717128:Reln protein, mouse; D012697:Serine Endopeptidases
keywords: Actin cytoskeleton; Cofilin phosphorylation; In utero electroporation; Neuronal migration; Reelin signaling