title: Brn3c null mutant mice show long-term, incomplete retention of some afferent inner ear innervation.
abstract: BACKGROUND
  Ears of Brn3c null mutants develop immature hair cells, identifiable only by certain molecular markers, and undergo apoptosis in neonates. This partial development of hair cells could lead to enough neurotrophin expression to sustain sensory neurons through embryonic development. We have therefore investigated in these mutants the patterns of innervation and of expression of known neurotrophins.
  
  
  RESULTS
  At birth there is a limited expression of BDNF and NT-3 in the mutant sensory epithelia and DiI tracing shows no specific reduction of afferents or efferents that resembles neurotrophin null mutations. At postnatal day 7/8 (P7/8), innervation is severely reduced both qualitatively and quantitatively. 1% of myosin VIIa-positive immature hair cells are present in the mutant cochlea, concentrated in the base. Around 20% of immature hair cells exist in the mutant vestibular sensory epithelia. Despite more severe loss of hair cells (1% compared to 20%), the cochlea retains many more sensory neurons (46% compared to 15%) than vestibular epithelia. Even 6 months old mutant mice have some fibers to all vestibular sensory epithelia and many more to the cochlear apex which lacks MyoVIIa positive hair cells. Topologically organized central cochlea projections exist at least until P8, suggesting that functional hair cells are not required to establish such projections.
  
  
  CONCLUSIONS
  The limited expression of neurotrophins in the cochlea of Brn3c null mice suffices to support many sensory neurons, particularly in the cochlea, until birth. The molecular nature of the long term survival of apical spiral neurons remains unclear.
authors.affiliation: Center for Advanced Biotechnology and Medicine, Department of Pediatrics, UMDNJ-Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA. xiang@cabm.rutgers.edu
authors.forename: Mengqing
authors.initials: M
authors.lastname: Xiang
authors.forename: Adel
authors.initials: A
authors.lastname: Maklad
authors.forename: Ulla
authors.initials: U
authors.lastname: Pirvola
authors.forename: Bernd
authors.initials: B
authors.lastname: Fritzsch
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002232:Carbocyanines; D002452:Cell Count / Q000379:methods; D004398:Dyneins / Q000378:metabolism; D007758:Ear, Inner / Q000254:growth & development / Q000294:innervation* / Q000473:pathology*; D004622:Embryo, Mammalian; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D006199:Hair Cells, Auditory, Inner / Q000378:metabolism*; D018398:Homeodomain Proteins; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D051379:Mice; D018345:Mice, Knockout; D018613:Microscopy, Confocal / Q000379:methods; D000081412:Myosin VIIa; D009218:Myosins / Q000378:metabolism; D009475:Neurons, Afferent / Q000378:metabolism / Q000502:physiology; D020933:Neurotrophin 3 / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013136:Spiral Ganglion / Q000166:cytology; D050821:Transcription Factor Brn-3C / Q000172:deficiency*
chemical_list: C035005:3,3'-dihexadecylindocarbocyanine; D019208:Brain-Derived Neurotrophic Factor; D002232:Carbocyanines; D018398:Homeodomain Proteins; C000631456:Myo7a protein, mouse; D000081412:Myosin VIIa; D020933:Neurotrophin 3; C121290:Pou4f3 protein, mouse; D012333:RNA, Messenger; D050821:Transcription Factor Brn-3C; D009218:Myosins; D004398:Dyneins