Document Detail


Correct timing of proliferation and differentiation is necessary for normal inner ear development and auditory hair cell viability.
MedLine Citation:
PMID:  23193000     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Benjamin J Kopecky; Israt Jahan; Bernd Fritzsch
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Developmental dynamics : an official publication of the American Association of Anatomists     Volume:  242     ISSN:  1097-0177     ISO Abbreviation:  Dev. Dyn.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-01-23     Completed Date:  2013-07-05     Revised Date:  2014-02-04    
Medline Journal Info:
Nlm Unique ID:  9201927     Medline TA:  Dev Dyn     Country:  United States    
Other Details:
Languages:  eng     Pagination:  132-47     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Wiley Periodicals, Inc.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Acoustic Stimulation
Animals
Cell Differentiation / physiology*
Cell Proliferation*
Ear, Inner / embryology*
Evoked Potentials, Auditory, Brain Stem / physiology
Gait / physiology
Genotype
Hair Cells, Auditory / physiology*
Immunohistochemistry
In Situ Hybridization
Integrases
Mice
Mice, Knockout
Microscopy, Confocal / methods
PAX2 Transcription Factor / metabolism
Phenylurea Compounds
Proto-Oncogene Proteins c-myc / genetics*
Regeneration / physiology*
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction / physiology*
Time Factors
Grant Support
ID/Acronym/Agency:
P30-DC010362/DC/NIDCD NIH HHS; R01 DC005590/DC/NIDCD NIH HHS; R01-DC055095590/DC/NIDCD NIH HHS; UL1RR024979/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Myc protein, mouse; 0/PAX2 Transcription Factor; 0/Pax2 protein, mouse; 0/Phenylurea Compounds; 0/Proto-Oncogene Proteins c-myc; 54924-46-8/ethylene diurea; EC 2.7.7.-/Cre recombinase; EC 2.7.7.-/Integrases
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Interstitial telomeric sequences are not preferentially involved in the chromosome damage induced by...
Next Document:  The characteristics of intramucosal bacteria in chronic rhinosinusitis: a prospective cross-sectiona...