title: Src controls neuronal migration by regulating the activity of FAK and cofilin.
abstract: Migration of postmitotic neurons in the developing cortex along radial glial fiber is essential for the formation of cortical layers. Several neurological diseases are caused by defects in neuronal migration, underlining the importance of this process for brain function. Multiple molecules are involved in this process. However, the precise mechanisms are largely unknown. In the present study, we examined the expression of Src in the developing cortex and investigated the role of Src in neuronal migration and its cellular and molecular mechanisms. Our results showed that Src was strongly expressed in the cerebral cortex during corticogenesis and mainly targeted to the leading processes of migrating neurons. Overexpression of wildtype Src (Src-WT) and its mutants, constitutively active Src (Src-CA) and dominant negative Src (Src-DN) in the mouse brain by in utero electroporation perturbed neuronal migration through affecting the adhesion properties and cytoskeletal dynamics of migrating neurons. Overexpression of Src-WT and Src-CA induced aggregation and branching of migrating neurons, whereas overexpression of Src-DN led to abnormal elongation of the leading processes of migrating neurons. Furthermore, we showed that Src activates the focal adhesion kinase (FAK) and cofilin by regulating their phosphorylation levels. We conclude that Src controls neuronal migration by regulating adhesion properties and F-actin dynamics of migrating neurons.
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, Yangling 712100, Shaanxi, PR China.
authors.forename: J T
authors.initials: JT
authors.lastname: Wang
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, Yangling 712100, Shaanxi, PR China.
authors.forename: L Z
authors.initials: LZ
authors.lastname: Song
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, Yangling 712100, Shaanxi, PR China.
authors.forename: L L
authors.initials: LL
authors.lastname: Li
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, Yangling 712100, Shaanxi, PR China.
authors.forename: W
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Institute for Structural Neurobiology, Center for Molecular Neurobiology Hamburg (ZMNH), University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: X J
authors.initials: XJ
authors.lastname: Chai
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, Yangling 712100, Shaanxi, PR China.
authors.forename: L
authors.initials: L
authors.lastname: An
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, Yangling 712100, Shaanxi, PR China.
authors.forename: S L
authors.initials: SL
authors.lastname: Chen
authors.affiliation: Institute for Structural Neurobiology, Center for Molecular Neurobiology Hamburg (ZMNH), University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Frotscher
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, Yangling 712100, Shaanxi, PR China. Electronic address: shantingzhao@hotmail.com.
authors.forename: S T
authors.initials: ST
authors.lastname: Zhao
mesh_terms: D051339:Actin Depolymerizing Factors / Q000378:metabolism*; D000199:Actins / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D002465:Cell Movement / Q000502:physiology*; D002540:Cerebral Cortex / Q000196:embryology* / Q000502:physiology; D018274:Electroporation; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism*; D018014:Gene Transfer Techniques; D057809:HEK293 Cells; D006801:Humans; D008810:Mice, Inbred C57BL; D009154:Mutation; D009474:Neurons / Q000502:physiology*; D010766:Phosphorylation / Q000502:physiology; D019061:src-Family Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D051339:Actin Depolymerizing Factors; D000199:Actins; D051417:Focal Adhesion Kinase 1; C496051:Ptk2 protein, mouse; D019061:src-Family Kinases
keywords: FAK; Src; cofilin; in utero electroporation; neuronal migration