Document Detail


In vivo proliferative regeneration of balance hair cells in newborn mice.
MedLine Citation:
PMID:  22573679     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The regeneration of mechanoreceptive hair cells occurs throughout life in non-mammalian vertebrates and allows them to recover from hearing and balance deficits that affect humans and other mammals permanently. The irreversibility of comparable deficits in mammals remains unexplained, but often has been attributed to steep embryonic declines in cellular production. However, recent results suggest that gravity-sensing hair cells in murine utricles may increase in number during neonatal development, raising the possibility that young mice might retain sufficient cellular plasticity for mitotic hair cell regeneration. To test for this we used neomycin to kill hair cells in utricles cultured from mice of different ages and found that proliferation increased tenfold in damaged utricles from the youngest neonates. To kill hair cells in vivo, we generated a novel mouse model that uses an inducible, hair cell-specific CreER allele to drive expression of diphtheria toxin fragment A (DTA). In newborns, induction of DTA expression killed hair cells and resulted in significant, mitotic hair cell replacement in vivo, which occurred days after the normal cessation of developmental mitoses that produce hair cells. DTA expression induced in 5-d-old mice also caused hair cell loss, but no longer evoked mitotic hair cell replacement. These findings show that regeneration limits arise in vivo during the postnatal period when the mammalian balance epithelium's supporting cells differentiate unique cytological characteristics and lose plasticity, and they support the notion that the differentiation of those cells may directly inhibit regeneration or eliminate an essential, but as yet unidentified pool of stem cells.
Authors:
Joseph C Burns; Brandon C Cox; Benjamin R Thiede; Jian Zuo; Jeffrey T Corwin
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of neuroscience : the official journal of the Society for Neuroscience     Volume:  32     ISSN:  1529-2401     ISO Abbreviation:  J. Neurosci.     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-05-10     Completed Date:  2012-07-06     Revised Date:  2013-06-25    
Medline Journal Info:
Nlm Unique ID:  8102140     Medline TA:  J Neurosci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  6570-7     Citation Subset:  IM    
Affiliation:
Department of Neuroscience, University of Virginia School of Medicine Charlottesville, VA 22908, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Animals, Newborn
Cell Proliferation*
Cells, Cultured
Female
Hair Cells, Auditory / cytology,  physiology*
Male
Mice
Neurogenesis / physiology*
Postural Balance / physiology*
Regeneration / physiology*
Saccule and Utricle / cytology,  physiology
Grant Support
ID/Acronym/Agency:
CA21765/CA/NCI NIH HHS; DC000200/DC/NIDCD NIH HHS; DC006471/DC/NIDCD NIH HHS; DC008800/DC/NIDCD NIH HHS; DC010310/DC/NIDCD NIH HHS; DC010519/DC/NIDCD NIH HHS; R01 DC000200/DC/NIDCD NIH HHS
Comments/Corrections

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


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