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

研究成果: Article査読

227 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)58-69
ページ数12
ジャーナルNeuron
77
1
DOI
出版ステータスPublished - 2013 1 9

ASJC Scopus subject areas

  • 神経科学(全般)

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