title: Aberrant expression of LIMK1 impairs neuronal migration during neocortex development.
abstract: Neuronal migration is essential for the formation of cortical layers, and proper neuronal migration requires the coordination of cytoskeletal regulation. LIMK1 is a serine/threonine protein kinase that mediates actin dynamics by regulating actin depolymerization factor/cofilin. However, the role of LIMK1 in neuronal migration and its potential mechanism remains elusive. Here, we found that using the in utero electroporation to overexpress LIMK1 and its mutants, constitutively active LIMK1 (LIMK1-CA) and dominant-negative LIMK1 (LIMK1-DN), impaired neuronal migration in the embryonic mouse brain. In addition, the aberrant expression of LIMK1-WT and LIMK1-CA induced abnormal branching and increased the length of the leading process, while LIMK1-DN-transfected neurons gave rise to two leading processes. Furthermore, the co-transfection of LIMK1-CA and cofilin-S3A partially rescued the migration deficiency and fully rescued the morphological changes in migrating neurons induced by LIMK1-CA. Our results indicated that LIMK1 negatively regulated neuronal migration by affecting the neuronal cytoskeleton and that its effects were partly mediated by cofilin phosphorylation.
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, No.22 Xinong Road, Yangling, 712100, Shaanxi, People's Republic of China.
authors.forename: Jiongfang
authors.initials: J
authors.lastname: Xie
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, No.22 Xinong Road, Yangling, 712100, Shaanxi, People's Republic of China.
authors.forename: Xuzhao
authors.initials: X
authors.lastname: Li
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, No.22 Xinong Road, Yangling, 712100, Shaanxi, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, No.22 Xinong Road, Yangling, 712100, Shaanxi, People's Republic of China.
authors.forename: Xuejun
authors.initials: X
authors.lastname: Chai
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, No.22 Xinong Road, Yangling, 712100, Shaanxi, People's Republic of China.
authors.forename: Yingxue
authors.initials: Y
authors.lastname: Huang
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, No.22 Xinong Road, Yangling, 712100, Shaanxi, People's Republic of China.
authors.forename: Kaikai
authors.initials: K
authors.lastname: Li
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, No.22 Xinong Road, Yangling, 712100, Shaanxi, People's Republic of China.
authors.forename: Xinran
authors.initials: X
authors.lastname: Cheng
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, No.22 Xinong Road, Yangling, 712100, Shaanxi, People's Republic of China. shantingzhao@hotmail.com.
authors.forename: Shanting
authors.initials: S
authors.lastname: Zhao
mesh_terms: D000818:Animals; D002465:Cell Movement; D020869:Gene Expression Profiling; D054461:Lim Kinases / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D019579:Neocortex / Q000196:embryology* / Q000473:pathology*; D009474:Neurons / Q000378:metabolism* / Q000473:pathology*
chemical_list: D054461:Lim Kinases; C515893:Limk1 protein, mouse
keywords: Actin cytoskeleton; Cofilin phosphorylation; In utero electroporation; LIMK1; Neuronal migration