Gene targeting reveals the role of Oc90 as the essential organizer of the otoconial organic matrix

Xing Zhao, Hua Yang, Ebenezer N. Yamoah, Yunxia Wang Lundberg

Research output: Contribution to journalArticle

53 Scopus citations

Abstract

A critical part of the functional development of our peripheral balance system is the embryonic formation of otoconia, composite crystals that overlie and provide optimal stimulus input to the sensory epithelium of the gravity receptor in the inner ear. To date neither the functions of otoconial proteins nor the processes of crystal formation are clearly defined. Using gene targeting and protein analysis strategies, we demonstrate that the predominant mammalian otoconin, otoconin-90/95 (Oc90), is essential for formation of the organic matrix of otoconia by specifically recruiting other matrix components, which includes otolin, a novel mammalian otoconin that we identified to be in wildtype murine otoconia. We show that this matrix controls otoconia growth and morphology by embedding the crystallites during seeding and growth. During otoconia development, the organic matrix forms prior to CaCO3 deposition and provides optimal calcification efficiency. Histological and ultrastructural examinations show normal inner ear epithelial morphology but reduced acellular matrices, including otoconial, cupular and tectorial membranes, in Oc90 null mice, likely due to an absence of Oc90 and a profound reduction of otolin. Our data demonstrate the critical roles of otoconins in otoconia seeding, growth and anchoring and suggest mechanistic similarities and differences between otoconia and bone calcification.

Original languageEnglish (US)
Pages (from-to)508-524
Number of pages17
JournalDevelopmental Biology
Volume304
Issue number2
DOIs
StatePublished - Apr 15 2007

Keywords

  • Calcification
  • Cupula
  • Fetuin-A
  • Otoconia
  • Otoconial membrane
  • Otoconin-90
  • Otolin
  • Tectorial membrane

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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