Lamellar projections in the endolymphatic sac act as a relief valve to regulate inner ear pressure

Elife. 2018 Jun 19:7:e37131. doi: 10.7554/eLife.37131.

Abstract

The inner ear is a fluid-filled closed-epithelial structure whose function requires maintenance of an internal hydrostatic pressure and fluid composition. The endolymphatic sac (ES) is a dead-end epithelial tube connected to the inner ear whose function is unclear. ES defects can cause distended ear tissue, a pathology often seen in hearing and balance disorders. Using live imaging of zebrafish larvae, we reveal that the ES undergoes cycles of slow pressure-driven inflation followed by rapid deflation. Absence of these cycles in lmx1bb mutants leads to distended ear tissue. Using serial-section electron microscopy and adaptive optics lattice light-sheet microscopy, we find a pressure relief valve in the ES comprised of partially separated apical junctions and dynamic overlapping basal lamellae that separate under pressure to release fluid. We propose that this lmx1-dependent pressure relief valve is required to maintain fluid homeostasis in the inner ear and other fluid-filled cavities.

Keywords: cell biology; developmental biology; inner ear; lamella; pressure; stem cells; timelapse; valve; zebrafish.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Embryo, Nonmammalian
  • Endolymphatic Sac / anatomy & histology
  • Endolymphatic Sac / physiology
  • Endolymphatic Sac / ultrastructure*
  • Female
  • Gene Expression
  • Hearing / physiology*
  • Homeostasis / physiology
  • Hydrostatic Pressure
  • In Situ Hybridization, Fluorescence
  • Larva / anatomy & histology
  • Larva / physiology
  • Larva / ultrastructure*
  • Male
  • Microscopy, Electron
  • Mutation
  • Time-Lapse Imaging
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism
  • Zebrafish
  • Zebrafish Proteins / genetics*
  • Zebrafish Proteins / metabolism

Substances

  • Transcription Factors
  • Zebrafish Proteins
  • lmx1bb protein, zebrafish