Atoh1 Directs the Formation of Sensory Mosaics and Induces Cell Proliferation in the Postnatal Mammalian Cochlea In Vivo

• Type of Material: Article
• Authors: Michael C. Kelly, Emory University; Qing Chang, Emory University; Alex Pan, Emory University; Xi Erick Lin, Emory University; Ping Helen Chen, Emory University
• Language: English
• Date: 2012-03-21
• Publisher: Society for Neuroscience
• Publication Version: Final Published Version
• Copyright Statement: © 2012 the authors
• License: Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported
• Final Published Version (URL): http://www.jneurosci.org/content/32/19/6699
• Title of Journal or Parent Work: Journal of Neuroscience Nursing
• ISSN: 0270-6474
• Volume: 32
• Issue: 19
• Start Page: 6699
• End Page: 6710
• Grant/Funding Information: The study was supported in part by the Neuronal Imaging Core of the Emory Neuroscience National Institute of Neurological Disorders and Stroke Core Facilities grant (P30NS055077).; This work was supported by National Institutes of Health (NIH)–National Institute on Deafness and Other Communication Disorders Grant R01 DC05213 and in part by the National Basic Research Program of China (973 Program) Grant 2012CB967902 and Natural Science Foundation of China Grant 81028003/H1305 (P.C.), and NIH–National Institute of General Medical Sciences Training Grant 5T32GM008605-12 (M.K.).
• Research Categories: Biology, Cell; Biology, Neuroscience

Abstract

Hearing impairment due to the loss of sensory hair cells is permanent in humans. Considerable interest targets the hair cell differentiation factor Atoh1 as a potential tool with which to promote hair cell regeneration. We generated a novel mouse model to direct the expression of Atoh1 in a spatially and temporally specific manner in the postnatal mammalian cochlea to determine the competency of various types of cochlear epithelial cells for hair cell differentiation. Atoh1 can generate cells in young animals with morphological, molecular, and physiological properties reminiscent of hair cells. This competency is cell type specific and progressively restricted with age. Significantly, Atoh1 induces ectopic sensory patches through Notch signaling to form a cellular mosaic similar to the endogenous sensory epithelia and expansion of the sensory mosaic through the conversion of supporting cells and nonautonomous supporting cell production. Furthermore, Atoh1 also activates proliferation within the normally postmitotic cochlear epithelium. These results provide insight into the potential and limitations of Atoh1-mediated hair cell regeneration.