title: Disruption of ephrin B/Eph B interaction results in abnormal cochlear innervation patterns.
abstract: OBJECTIVE
  To determine the expression patterns of B ephrins and Ephs in the cochlea and identify functional consequences of disruption of ephrin B/Eph B interactions in both cultured spiral ganglion neurons and in the cochlea of live animals.
  
  
  METHODS
  The expression patterns of various B ephrins and Ephs were determined in mice with Lac-Z mutation. Mice with null function of individual B ephrin and Eph proteins and those with multiple knockouts were studied for cochlear innervation patterns.
  
  
  METHODS
  Mice with B ephrins and Ephs disrupted with the β-galactosidase gene were sacrificed at P6, and their cochleae isolated and processed for Lac-Z staining to determine expression of these proteins in cochlear tissue. Spiral ganglion cells from wild-type as well as ephrin B1 knockout mice were isolated and cocultured with Eph B2 expressing Cos1 cells and neurite lengths were determined. Fluorescent lipophillic dyes were used to label spiral ganglion cell nerve fibers to determine cochlear innervation patterns in wild-type and knockout mice.
  
  
  RESULTS
  Eph B1, B2, and ephrin B2 but not B3 was expressed in the cochlea. Eph B2 inhibited outgrowth of spiral ganglion cell axons from wild-type mice, but not from ephrin B1 knockout mice in culture. Knockout mice with null function of ephrin B1 alone or Eph B1, Eph B2, Eph B3 in combination demonstrated abnormal innervation patterns in the organ of Corti.
  
  
  CONCLUSIONS
  Disruption of B ephrins and Ephs results in functional consequences in spiral ganglion cells, suggesting that these proteins play a role in establishing normal innervation patterns in the cochlea.
authors.affiliation: Department of Otolaryngology-Head & Neck Surgery, University of Texas Southwestern Medical Center at Dallas, Division of Pediatric Otolaryngology, Children's Medical Center, Dallas, and Dallas Cochlear Implant Program, Dallas, Texas 75390-9035, USA. Kenneth.Lee@UTSouthwestern.edu
authors.forename: Constance Q
authors.initials: CQ
authors.lastname: Zhou
authors.forename: James
authors.initials: J
authors.lastname: Lee
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Henkemeyer
authors.forename: Kenneth H
authors.initials: KH
authors.lastname: Lee
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015415:Biomarkers / Q000378:metabolism; D003051:Cochlea / Q000294:innervation* / Q000378:metabolism*; D003056:Cochlear Nerve / Q000378:metabolism* / Q000502:physiology; D036387:Ephrin-B1 / Q000235:genetics / Q000378:metabolism*; D036388:Ephrin-B2 / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D051379:Mice; D018345:Mice, Knockout; D023421:Models, Animal; D011897:Random Allocation; D036081:Receptors, Eph Family / Q000235:genetics / Q000378:metabolism*; D012680:Sensitivity and Specificity; D015398:Signal Transduction; D013136:Spiral Ganglion / Q000378:metabolism / Q000502:physiology; D013701:Temporal Bone / Q000378:metabolism
chemical_list: D015415:Biomarkers; D036387:Ephrin-B1; D036388:Ephrin-B2; D036081:Receptors, Eph Family