2012
DOI: 10.1523/jneurosci.0818-12.2012
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Abstract: Unlike non-mammalian vertebrates, mammals cannot convert inner ear cochlear supporting cells (SCs) into sensory hair cells (HCs) after damage, thus causing permanent deafness. Here, we achieved in vivo conversion of two SC subtypes, pillar cells (PCs) and Deiters’ cells (DCs), into HCs by inducing targeted expression of Atoh1 at neonatal and juvenile ages using novel mouse models. The conversion only occurred in ~10% of PCs and DCs with ectopic Atoh1 expression and started with reactivation of endogenous Atoh1… Show more

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Cited by 179 publications
(307 citation statements)
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“…The present findings also provide a framework for interpreting our previous observation that ectopic Atoh1 overexpression in IBCs and IPhCs in the neonatal cochlea converts them into HCs without altering organ of Corti morphology (54,55). Based on our current findings, we propose that, after the original IBCs/IPhCs convert to HCs due to Atoh1 expression, they are replenished rapidly by transdifferentiation of GER cells.…”
Section: Discussionsupporting
confidence: 79%
See 1 more Smart Citation
“…The present findings also provide a framework for interpreting our previous observation that ectopic Atoh1 overexpression in IBCs and IPhCs in the neonatal cochlea converts them into HCs without altering organ of Corti morphology (54,55). Based on our current findings, we propose that, after the original IBCs/IPhCs convert to HCs due to Atoh1 expression, they are replenished rapidly by transdifferentiation of GER cells.…”
Section: Discussionsupporting
confidence: 79%
“…GER cells are immediate neighbors of IBCs, IPhCs, and IHCs and may be less differentiated than SCs in the organ of Corti. GER cells exhibit higher levels of Wnt signaling (e.g., β-catenin and Lgr5) (38)(39)(40)52) and lower levels of Notch signaling (53) and respond readily to Atoh1 (atonal homolog 1) ectopic expression (54)(55)(56)(57). GER cells also express Nestin, a stem/progenitor cell marker in the central nervous system (58).…”
Section: Discussionmentioning
confidence: 99%
“…Indeed, immature mouse pillar cells can be induced in cultured cochleae to convert to hair cells when both Notch and FGF signaling are blocked (Doetzlhofer et al 2009), and following noise damage, Notch inhibition in vivo has a limited ability to convert residual cochlear support cells into functional hair cells (Mizutari et al 2013). Furthermore, induced expression of Atoh1 in immature but not mature Deiters' cells promotes hair cell differentiation (Liu et al 2012). Interestingly, mature Deiters' cells continue to express Fgfr3 well past the stage when cochlear FGF expression is extinguished (Hayashi et al 2010).…”
Section: Discussionmentioning
confidence: 99%
“…However, this ability is confined to early developmental stages, with the competence of the inner ear epithelium to respond to Atoh1 strongly tapering off shortly after birth (19,20). A second temporal aspect is that although Atoh1 is best described for its role in early hair cell specification, temporally controlled knock-out studies have suggested that it is also involved in later aspects of hair cell differentiation and survival (10,21).…”
Section: Context Dependence Of Atoh1mentioning
confidence: 99%