EphB2 Guides Axons at the Midline and Is Necessary for Normal Vestibular Function

Neuron. 2000 May;26(2):417-30. doi: 10.1016/s0896-6273(00)81174-5.

Abstract

Mice lacking the EphB2 receptor tyrosine kinase display a cell-autonomous, strain-specific circling behavior that is associated with vestibular phenotypes. In mutant embryos, the contralateral inner ear efferent growth cones exhibit inappropriate pathway selection at the midline, while in mutant adults, the endolymph-filled lumen of the semicircular canals is severely reduced. EphB2 is expressed in the endolymph-producing dark cells in the inner ear epithelium, and these cells show ultrastructural defects in the mutants. A molecular link to fluid regulation is provided by demonstrating that PDZ domain-containing proteins that bind the C termini of EphB2 and B-ephrins can also recognize the cytoplasmic tails of anion exchangers and aquaporins. This suggests EphB2 may regulate ionic homeostasis and endolymph fluid production through macromolecular associations with membrane channels that transport chloride, bicarbonate, and water.

Publication types

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

MeSH terms

  • Animals
  • Axons / physiology*
  • Cochlear Nerve / embryology
  • Ear, Inner / innervation
  • Embryo, Mammalian / metabolism
  • Endolymph / metabolism
  • Growth Cones / physiology
  • Mice
  • Mutation / physiology
  • Neurons, Efferent / physiology
  • Receptor Protein-Tyrosine Kinases / genetics
  • Receptor Protein-Tyrosine Kinases / physiology*
  • Receptor, EphB2
  • Rhombencephalon / embryology
  • Semicircular Canals / abnormalities
  • Stereotypic Movement Disorder / genetics
  • Vestibular Nerve / embryology
  • Vestibule, Labyrinth / embryology
  • Vestibule, Labyrinth / innervation
  • Vestibule, Labyrinth / physiopathology

Substances

  • Receptor Protein-Tyrosine Kinases
  • Receptor, EphB2