Molecular mechanisms underlying ectopic otoconia-like particles in the endolymphatic sac of embryonic mice

Elena G. Ignatova, Isolde Thalmann, Baogang Xu, David M. Ornitz, Ruediger Thalmann

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

Otoconin-90, the principal otoconial matrix protein, provided a tool to investigate the molecular mechanism of otoconial morphogenesis. The endolymphatic sac of the embryonic chick and guinea pig contain otoconia. Here, we show that the embryonic mouse transiently expresses ectopic otoconia in the endolymphatic sac. Massive precipitate of otoconin-90-positive material is detectable in the lumen of the endolymphatic sac between embryonic day 14.5 and 17.5 with frequent accretion into more heavily staining otoconia-like particles. Otoconin-90 was also localized at the surface and the interior of epithelial cells lining the endolymphatic sac as well as incorporated into free floating cells. In contrast, in situ hybridization failed to detect mRNA in the endolymphatic duct and sac, even though the adjacent nonsensory vestibular structures are heavily stained. Because of ample expression of otoconin-90 protein in the absence of the corresponding mRNA, we conclude that the luminal otoconin-90 is imported via longitudinal flow from the vestibular compartments, where both mRNA and protein are strongly expressed. Because of absence of mRNA, the expression of the corresponding protein by the epithelia lining the endolymphatic sac can only be explained by a resorptive process, as previously proposed on the basis of the movement of luminal macromolecules. The data do not support the previous hypothesis that the transient expression of otoconia-like particles of the endolymphatic sac represents a vestigial phenomenon from the amphibian stage, since amphibia express ample mRNA encoding otoconin-22 in the endolymphatic sac system.

Original languageEnglish
Pages (from-to)65-72
Number of pages8
JournalHearing research
Volume194
Issue number1-2
DOIs
StatePublished - Aug 2004

Keywords

  • ED - embryonic day
  • ES - endolymphatic sac
  • Endolymphatic sac
  • HS - homogeneous substance
  • OC90 - otoconin-90
  • Otoconia
  • Otoconin-90
  • PND - postnatal day
  • het - head tilt
  • kDa - kilodalton

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