title: Aberrant cochlear hair cell attachments caused by Nectin-3 deficiency result in hair bundle abnormalities.
abstract: The organ of Corti consists of sensory hair cells (HCs) interdigitated with nonsensory supporting cells (SCs) to form a checkerboard-like cellular pattern. HCs are equipped with hair bundles on their apical surfaces. We previously reported that cell-adhesive nectins regulate the checkerboard-like cellular patterning of HCs and SCs in the mouse auditory epithelium. Nectin-1 and -3 are differentially expressed in normal HCs and SCs, respectively, and in Nectin-3-deficient mice a number of HCs are aberrantly attached to each other. We show here that these aberrantly attached HCs in Nectin-3-deficient mice, but not unattached ones, show disturbances of the orientation and morphology of the hair bundles and the positioning of the kinocilium, with additional abnormal localisation of cadherin-catenin complexes and the apical-basal polarity proteins Pals1 and Par-3. These results indicate that, owing to the loss of Nectin-3, hair cells contact each other inappropriately and form abnormal junctions, ultimately resulting in abnormal hair bundle orientation and morphology.
authors.affiliation: Division of Molecular and Cellular Biology, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
authors.forename: Terunobu
authors.initials: T
authors.lastname: Fukuda
authors.forename: Kanoko
authors.initials: K
authors.lastname: Kominami
authors.forename: Shujie
authors.initials: S
authors.lastname: Wang
authors.forename: Hideru
authors.initials: H
authors.lastname: Togashi
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Hirata
authors.forename: Akira
authors.initials: A
authors.lastname: Mizoguchi
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Rikitake
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Takai
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D016764:Cell Polarity; D005260:Female; D051157:Frizzled Receptors / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006198:Hair Cells, Auditory / Q000378:metabolism* / Q000473:pathology*; D007365:Intercellular Junctions / Q000378:metabolism / Q000473:pathology; D007760:Labyrinth Supporting Cells / Q000378:metabolism / Q000473:pathology; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D000075983:Nectins; D009925:Organ of Corti / Q000002:abnormalities* / Q000196:embryology / Q000378:metabolism*; D011247:Pregnancy
chemical_list: D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; D051157:Frizzled Receptors; C111048:Fzd6 protein, mouse; D008565:Membrane Proteins; C000619015:Nectin1 protein, mouse; C000619017:Nectin3 protein, mouse; D000075983:Nectins; C528120:Vangl1 protein, mouse
keywords: Cell adhesion; Mouse; Nectin; Polarity