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

Content Provider	PubMed Central
Author	Mizutari, Kunio Fujioka, Masato Hosoya, Makoto Bramhall, Naomi Okano, Hirotaka James Okano, Hideyuki Edge, Albert S. B.
Copyright Year	2012
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.
Related Links	http://dx.doi.org/10.1016/j.neuron.2012.10.032
Ending Page	69
Page Count	12
Starting Page	58
File Format	PDF
ISSN	08966273
e-ISSN	10974199
Journal	Neuron
Issue Number	1
Volume Number	77
Language	English
Publisher Date	2013-01-01
Access Restriction	Open
Subject Keyword	Neuroscience(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Neuroscience

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