title: Jagged1-mediated Notch signaling regulates mammalian inner ear development independent of lateral inhibition.
abstract: CONCLUSIONS
  Jagged1-mediated Notch signaling regulates hair cell (HC) production in a distinct way rather than lateral inhibition mediated by Hes1 and Hes5. Jagged1 may interact with Notch3, probably via candidate downstream mediators Hesr1 and Hesr2, regulating the prosensory formation in the early stage.
  
  
  OBJECTIVE
  To explore the function of the Jagged1-mediated Notch signaling pathway in mammalian inner ear development and its possible mechanism.
  
  
  METHODS
  Using conditional gene targeting, a novel Jagged1 conditional knockout (Jag1-cko), Pax8(cre/+); Jag1(flox/flox), was established. The auditory brainstem response and swim ability test were utilized to identify functional disability. The expression of Jagged1, Notch3, Hes1, Hesr1, and Hesr2 was detected by immunofluorescence and immunohistochemistry.
  
  
  RESULTS
  Our Jag1-cko model was established and survived well. It presented hearing impairment and balance disturbance with 'waltzing' behavior. Cochleae and vestibular apparatus were all found in our Jag1-cko model. Patch deficiency of outer hair cells (OHCs) was found on the apical and middle turns of the auditory epithelium. OHCs were totally missing on the basal turn. The stereociliary bundles were disorientated on the cristae. Unlike Hes1, no expression of Notch3, Hesr1, and Hesr2 was found on embryonic day 13.5 of the Jag1-cko model.
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, PR China.
authors.forename: Jin
authors.initials: J
authors.lastname: Hao
authors.forename: Robert
authors.initials: R
authors.lastname: Koesters
authors.forename: Maxime
authors.initials: M
authors.lastname: Bouchard
authors.forename: Thomas
authors.initials: T
authors.lastname: Gridley
authors.forename: Susanna
authors.initials: S
authors.lastname: Pfannenstiel
authors.forename: Peter K
authors.initials: PK
authors.lastname: Plinkert
authors.forename: Luo
authors.initials: L
authors.lastname: Zhang
authors.forename: Mark
authors.initials: M
authors.lastname: Praetorius
mesh_terms: D000818:Animals; D002135:Calcium-Binding Proteins / Q000235:genetics*; D007758:Ear, Inner / Q000196:embryology*; D016057:Evoked Potentials, Auditory, Brain Stem; D018507:Gene Expression Regulation, Developmental; D006198:Hair Cells, Auditory / Q000378:metabolism* / Q000502:physiology; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D000072100:Jagged-1 Protein; D008322:Mammals / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D023421:Models, Animal; D016133:Polymerase Chain Reaction / Q000379:methods; D051880:Receptors, Notch / Q000235:genetics* / Q000378:metabolism; D012016:Reference Values; D012680:Sensitivity and Specificity; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology
chemical_list: D002135:Calcium-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; C000606274:Jag1 protein, mouse; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; D051880:Receptors, Notch; D000072099:Serrate-Jagged Proteins