Age-DependentIn VivoConversion of Mouse Cochlear Pillar and Deiters' Cells to Immature Hair Cells by Atoh1 Ectopic Expression

• DOI: 10.1523/jneurosci.0818-12.2012
• Publication Date: 2012-05-09T17:01:26Z
• Authors: Zhiyong Liu; Jennifer A. Dearman; Brandon C. Cox; Brandon J. Walters; Lingli Zhang; Olivier Ayrault; Frederique Zindy; Lin Gan; Martine F. Roussel; Jian Zuo
• Keywords: Ectopic expression

Unlike nonmammalian vertebrates, mammals cannot convert inner ear cochlear supporting cells (SCs) into sensory hair (HCs) after damage, thus causing permanent deafness. Here, we achieved in vivo conversion of two SC subtypes, pillar (PCs) and Deiters' (DCs), HCs by inducing targeted expression Atoh1 at neonatal juvenile ages using novel mouse models. The only occurred ∼10% PCs DCs with ectopic started reactivation endogenous followed 11 HC synaptic markers, a process that took approximately 3 weeks vivo. These new resided the outer region, formed stereocilia, contained mechanoelectrical transduction channels, survived for >2 months vivo; however, they surprisingly lacked prestin oncomodulin mature morphology. In contrast, adult no longer responded to expression, even damage. Finally, did not affect but caused cell loss HCs. Together, our results demonstrate immature is age dependent resembles normal development. Therefore, combined additional factors holds therapeutic promise functional regenerative purposes.