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Author Notes:

Correspondence should be addressed to Ping Chen, Department of Cell Biology, Emory University, 615 Michael Street, Atlanta, GA 30322., ping.chen@emory.edu

Author contributions: M.C.K., Q.C., X.L., and P.C.

Designed research; M.C.K., Q.C., and A.P. performed research; M.C.K., X.L., and P.C. contributed unpublished reagents/analytic tools; M.C.K., Q.C., A.P., X.L., and P.C. analyzed data; M.C.K., Q.C., and P.C. wrote the paper.

The authors declare no competing financial interests.

The Emory transgenic core staff assisted with generation of the TgAtoh1 mouse line.

We thank the members of the Chen laboratory for helpful discussion, Dr. Yibo Huang for assistance with some of the experiments, Dr. Amy Kiernan for advice on doxycycline administration, Dr. James Bartle for the Espin antibody, and Dr. Jian Zuo and Dr. Zhiyong Liu for critical review of the manuscript.

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Research Funding:

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.).

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).

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

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Journal Title:

Journal of Neuroscience Nursing

Volume:

Volume 32, Number 19

Publisher:

, Pages 6699-6710

Type of Work:

Article | Final Publisher PDF

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.

Copyright information:

© 2012 the authors

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License (http://creativecommons.org/licenses/by-nc-sa/3.0/).

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