title: FilaminB is required for the directed localization of cell-cell adhesion molecules in embryonic epithelial development.
abstract: Filamin proteins cross-link F-actin and form a scaffold for numerous signal transduction systems. In this study, we show that filaminB is apically enriched in avian embryonic epithelium, and colocalizes with cell adhesion molecules and circumferential F-actin. FilaminB knockdown in the neural tube and somites decreases the accumulation of N-cadherin and ZO-1 protein at cell junctions, and promotes disruption of these tissues and the presence of neuronal aggregates within the lumen of the neural tube. This phenotype resembles that of human congenital condition, periventricular heterotopia (PH). FilaminB knockdown in MDCK cells suggests that filaminB is required for the apical accumulation of adhesion molecules in the junctional complex and subsequent epithelium formation. We further suggest that the reduction of structural integrity of the neural epithelium caused by the loss of Filamin function may also result in formation of the neuronal nodules found in PH patients.
authors.affiliation: Tohoku University, Graduate School of Medicine, Center for Translational and Advanced Animal Research on Human Diseases, Division of Developmental Neuroscience, Sendai, Miyagi, Japan. wakasama@med.tohoku.ac.jp
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Wakamatsu
authors.forename: Daisuke
authors.initials: D
authors.lastname: Sakai
authors.forename: Takashi
authors.initials: T
authors.lastname: Suzuki
authors.forename: Noriko
authors.initials: N
authors.lastname: Osumi
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000235:genetics; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002478:Cells, Cultured; D002642:Chick Embryo; D003285:Contractile Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D003370:Coturnix / Q000196:embryology / Q000235:genetics; D004285:Dogs; D004625:Embryo, Nonmammalian; D047108:Embryonic Development / Q000235:genetics / Q000502:physiology; D004848:Epithelium / Q000196:embryology* / Q000378:metabolism; D064448:Filamins; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D009420:Nervous System / Q000196:embryology / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000502:physiology; D021381:Protein Transport; D019170:Somites / Q000196:embryology / Q000378:metabolism
chemical_list: D015815:Cell Adhesion Molecules; D003285:Contractile Proteins; D064448:Filamins; D008840:Microfilament Proteins; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins