Aberrant cochlear hair cell attachments caused by Nectin-3 deficiency result in hair bundle abnormalities

Development. 2014 Jan;141(2):399-409. doi: 10.1242/dev.094995.

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.

Keywords: Cell adhesion; Mouse; Nectin; Polarity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carrier Proteins / metabolism
  • Cell Adhesion
  • Cell Adhesion Molecules / deficiency*
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism
  • Cell Polarity
  • Female
  • Frizzled Receptors / metabolism
  • Gene Expression Regulation, Developmental
  • Hair Cells, Auditory / metabolism*
  • Hair Cells, Auditory / pathology*
  • Intercellular Junctions / metabolism
  • Intercellular Junctions / pathology
  • Labyrinth Supporting Cells / metabolism
  • Labyrinth Supporting Cells / pathology
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Knockout
  • Microscopy, Electron, Scanning
  • Microscopy, Electron, Transmission
  • Nectins
  • Organ of Corti / abnormalities*
  • Organ of Corti / embryology
  • Organ of Corti / metabolism*
  • Pregnancy

Substances

  • Carrier Proteins
  • Cell Adhesion Molecules
  • Frizzled Receptors
  • Fzd6 protein, mouse
  • Membrane Proteins
  • Nectin1 protein, mouse
  • Nectin3 protein, mouse
  • Nectins
  • Vangl1 protein, mouse