Notch Inhibition Induces Cochlear Hair Cell Regeneration and Recovery of Hearing after Acoustic Trauma

Kunio Mizutari, Masato Fujioka, Makoto Hosoya, Naomi Bramhall, Hirotaka James Okano, Hideyuki Okano, Albert S B Edge

Research output: Contribution to journalArticle

183 Citations (Scopus)

Abstract

Hearing loss due to damage to auditory hair cells is normally irreversible because mammalian hair cells do not regenerate. Here, we show that new hair cells can be induced and can cause partial recovery of hearing in ears damaged by noise trauma, when Notch signaling is inhibited by a γ-secretase inhibitor selected for potency in stimulating hair cell differentiation from inner ear stem cells in vitro. Hair cell generation resulted from an increase in the level of bHLH transcription factor Atoh1 in response to inhibition of Notch signaling. In vivo prospective labeling of Sox2-expressing cells with a Cre-lox system unambiguously demonstrated that hair cell generation resulted from transdifferentiation of supporting cells. Manipulating cell fate of cochlear sensory cells in vivo by pharmacological inhibition of Notch signaling is thus a potential therapeutic approach to the treatment of deafness.

Original languageEnglish
Pages (from-to)58-69
Number of pages12
JournalNeuron
Volume77
Issue number1
DOIs
Publication statusPublished - 2013 Jan 9

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Auditory Hair Cells
Noise-Induced Hearing Loss
Hearing
Regeneration
Cell Transdifferentiation
Basic Helix-Loop-Helix Transcription Factors
Amyloid Precursor Protein Secretases
Cochlea
Deafness
Inner Ear
Inhibition (Psychology)
Hearing Loss
Ear
Noise
Cell Differentiation
Stem Cells
Pharmacology

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Notch Inhibition Induces Cochlear Hair Cell Regeneration and Recovery of Hearing after Acoustic Trauma. / Mizutari, Kunio; Fujioka, Masato; Hosoya, Makoto; Bramhall, Naomi; Okano, Hirotaka James; Okano, Hideyuki; Edge, Albert S B.

In: Neuron, Vol. 77, No. 1, 09.01.2013, p. 58-69.

Research output: Contribution to journalArticle

Mizutari, Kunio ; Fujioka, Masato ; Hosoya, Makoto ; Bramhall, Naomi ; Okano, Hirotaka James ; Okano, Hideyuki ; Edge, Albert S B. / Notch Inhibition Induces Cochlear Hair Cell Regeneration and Recovery of Hearing after Acoustic Trauma. In: Neuron. 2013 ; Vol. 77, No. 1. pp. 58-69.
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