Correct Timing of Proliferation and Differentiation is Necessary for Normal Inner Ear Development and Auditory Hair Cell Viability
Article first published online: 22 JAN 2013
Copyright © 2012 Wiley Periodicals, Inc.
Volume 242, Issue 2, pages 132–147, February 2013
How to Cite
Kopecky, B. J., Jahan, I. and Fritzsch, B. (2013), Correct Timing of Proliferation and Differentiation is Necessary for Normal Inner Ear Development and Auditory Hair Cell Viability. Dev. Dyn., 242: 132–147. doi: 10.1002/dvdy.23910
- Issue published online: 22 JAN 2013
- Article first published online: 22 JAN 2013
- Accepted manuscript online: 29 NOV 2012 04:57AM EST
- Manuscript Accepted: 18 NOV 2012
- Manuscript Received: 26 APR 2012
- NIH. Grant Number: P30-DC010362
- NIDCD. Grant Number: R01-DC055095590
- CTSA. Grant Number: UL1RR024979
- hair cell;
Background: Hearing restoration through hair cell regeneration will require revealing the dynamic interactions between proliferation and differentiation during development to avoid the limited viability of regenerated hair cells. Pax2-Cre N-Myc conditional knockout (CKO) mice highlighted the need of N-Myc for proper neurosensory development and possible redundancy with L-Myc. The late-onset hair cell death in the absence of early N-Myc expression could be due to mis-regulation of genes necessary for neurosensory formation and maintenance, such as Neurod1, Atoh1, Pou4f3, and Barhl1. Results: Pax2-Cre N-Myc L-Myc double CKO mice show that proliferation and differentiation are linked together through Myc and in the absence of both Mycs, altered proliferation and differentiation result in morphologically abnormal ears. In particular, the organ of Corti apex is re-patterned into a vestibular-like organization and the base is truncated and fused with the saccule. Conclusions: These data indicate that therapeutic approaches to restore hair cells must take into account a dynamic interaction of proliferation and differentiation regulation of basic Helix-Loop-Helix transcription factors in attempts to stably replace lost cochlear hair cells. In addition, our data indicate that Myc is an integral component of the evolutionary transformation process that resulted in the organ of Corti development. Developmental Dynamics 242:132–147, 2013. © 2012 Wiley Periodicals, Inc.