title: Hox2 Genes Are Required for Tonotopic Map Precision and Sound Discrimination in the Mouse Auditory Brainstem.
abstract: Tonotopy is a hallmark of auditory pathways and provides the basis for sound discrimination. Little is known about the involvement of transcription factors in brainstem cochlear neurons orchestrating the tonotopic precision of pre-synaptic input. We found that in the absence of Hoxa2 and Hoxb2 function in Atoh1-derived glutamatergic bushy cells of the anterior ventral cochlear nucleus, broad input topography and sound transmission were largely preserved. However, fine-scale synaptic refinement and sharpening of isofrequency bands of cochlear neuron activation upon pure tone stimulation were impaired in Hox2 mutants, resulting in defective sound-frequency discrimination in behavioral tests. These results establish a role for Hox factors in tonotopic refinement of connectivity and in ensuring the precision of sound transmission in the mammalian auditory circuit.
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland; University of Basel, 4003 Basel, Switzerland.
authors.forename: Kajari
authors.initials: K
authors.lastname: Karmakar
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Narita
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Fadok
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland.
authors.forename: Sebastien
authors.initials: S
authors.lastname: Ducret
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland; University of Basel, 4003 Basel, Switzerland.
authors.forename: Alberto
authors.initials: A
authors.lastname: Loche
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland.
authors.forename: Taro
authors.initials: T
authors.lastname: Kitazawa
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland.
authors.forename: Christel
authors.initials: C
authors.lastname: Genoud
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Di Meglio
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland.
authors.forename: Raphael
authors.initials: R
authors.lastname: Thierry
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland.
authors.forename: Joao
authors.initials: J
authors.lastname: Bacelo
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland; University of Basel, 4003 Basel, Switzerland.
authors.forename: Andreas
authors.initials: A
authors.lastname: Lüthi
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland; University of Basel, 4003 Basel, Switzerland. Electronic address: filippo.rijli@fmi.ch.
authors.forename: Filippo M
authors.initials: FM
authors.lastname: Rijli
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001301:Audiometry, Pure-Tone; D001306:Auditory Pathways / Q000502:physiology*; D001307:Auditory Perception / Q000502:physiology*; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D001933:Brain Stem / Q000502:physiology*; D002448:Cell Adhesion; D017626:Cochlear Nucleus / Q000502:physiology; D003213:Conditioning, Psychological; D005239:Fear; D020869:Gene Expression Profiling; D005971:Glutamates / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation / Q000235:genetics; D009474:Neurons / Q000378:metabolism; D038081:Organogenesis / Q000235:genetics; D013569:Synapses / Q000378:metabolism / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D005971:Glutamates; D018398:Homeodomain Proteins; D014157:Transcription Factors; C500943:Atoh1 protein, mouse; C489833:Hoxa2 protein, mouse; C490111:Hoxb2 protein, mouse
keywords: auditory circuit refinement; brainstem auditory nuclei development; bushy cells; endbulb of held; glutamatergic cochlear neurons; homeodomain transcription factors; sound frequency discrimination; tonotopic map formation