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Correct Timing of Proliferation and Differentiation is Necessary for Normal Inner Ear Development and Auditory Hair Cell Viability
Author(s) -
Kopecky Benjamin J.,
Jahan Israt,
Fritzsch Bernd
Publication year - 2013
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/dvdy.23910
Subject(s) - organ of corti , hair cell , biology , inner ear , cochlea , microbiology and biotechnology , saccule , conditional gene knockout , cellular differentiation , transcription factor , cell growth , anatomy , genetics , gene , phenotype
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 Myc s , 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.