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

TY - JOUR

T1 - Reelin and cofilin cooperate during the migration of cortical neurons: a quantitative morphological analysis

AU - Chai, Xuejun

AU - Zhao, Shanting

AU - Fan, Li

AU - Zhang, Wei

AU - Lu, Xi

AU - Shao, Hong

AU - Wang, Shaobo

AU - Song , Lingzhen

AU - Failla, Antonio Virgilio

AU - Zobiak, Bernd

AU - Mannherz, Hans G

AU - Frotscher, Michael

N1 - © 2016. Published by The Company of Biologists Ltd.

PY - 2016/3/15

Y1 - 2016/3/15

N2 - 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.

AB - 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.

KW - Animals

KW - Cell Adhesion Molecules, Neuronal

KW - Cell Count

KW - Cell Movement

KW - Cell Shape

KW - Cerebral Cortex

KW - Cofilin 1

KW - Electroporation

KW - Embryo, Mammalian

KW - Extracellular Matrix Proteins

KW - Female

KW - Mice, Inbred C57BL

KW - Nerve Tissue Proteins

KW - Neurons

KW - Serine Endopeptidases

KW - Transfection

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1242/dev.134163

DO - 10.1242/dev.134163

M3 - SCORING: Journal article

C2 - 26893343

VL - 143

SP - 1029

EP - 1040

JO - DEVELOPMENT

JF - DEVELOPMENT

SN - 0950-1991

IS - 6

ER -