A tectorin-based matrix and planar cell polarity genes are required for normal collagen-fibril orientation in the developing tectorial membrane

Development. 2017 Nov 1;144(21):3978-3989. doi: 10.1242/dev.151696. Epub 2017 Sep 21.

Abstract

The tectorial membrane is an extracellular structure of the cochlea. It develops on the surface of the auditory epithelium and contains collagen fibrils embedded in a tectorin-based matrix. The collagen fibrils are oriented radially with an apically directed slant - a feature considered crucial for hearing. To determine how this pattern is generated, collagen-fibril formation was examined in mice lacking a tectorin-based matrix, epithelial cilia or the planar cell polarity genes Vangl2 and Ptk7 In wild-type mice, collagen-fibril bundles appear within a tectorin-based matrix at E15.5 and, as fibril number rapidly increases, become co-aligned and correctly oriented. Epithelial width measurements and data from Kif3acKO mice suggest, respectively, that radial stretch and cilia play little, if any, role in determining normal collagen-fibril orientation; however, evidence from tectorin-knockout mice indicates that confinement is important. PRICKLE2 distribution reveals the planar cell polarity axis in the underlying epithelium is organised along the length of the cochlea and, in mice in which this polarity is disrupted, the apically directed collagen offset is no longer observed. These results highlight the importance of the tectorin-based matrix and epithelial signals for precise collagen organisation in the tectorial membrane.

Keywords: Cochlea; Collagen; Hearing; Inner ear; Planar cell polarity; Tectorial membrane.

MeSH terms

  • Animals
  • Cell Polarity / genetics*
  • Cilia / metabolism
  • Cilia / ultrastructure
  • Epithelium / embryology
  • Epithelium / metabolism
  • Extracellular Matrix / genetics*
  • Extracellular Matrix Proteins / metabolism*
  • Fibrillar Collagens / metabolism*
  • GPI-Linked Proteins / metabolism
  • LIM Domain Proteins / metabolism
  • Membrane Proteins / metabolism*
  • Mice, Knockout
  • Models, Biological
  • Organ of Corti / metabolism
  • Tectorial Membrane / embryology*
  • Tectorial Membrane / metabolism*
  • Tectorial Membrane / ultrastructure

Substances

  • Extracellular Matrix Proteins
  • Fibrillar Collagens
  • GPI-Linked Proteins
  • LIM Domain Proteins
  • Membrane Proteins
  • Prickle2 protein, mouse
  • Tecta protein, mouse
  • beta-tectorin, mouse