Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2008-6-18
pubmed:abstractText
In the vestibular organs of the inner ear, an early postnatal decline in the capacity for cell proliferation appears to be responsible for limits to hair cell regeneration that are unique to mammals. We have investigated the time course of that decline in cell proliferation and its potential regulation by glycogen synthase kinase-3 (GSK3). Our immunoblots have revealed that inactive GSK3 beta decreases postnatally in the murine utricular epithelium, as E-cadherin and the active forms of GSK3 alpha and GSK3 beta each increase. In cultured utricular epithelia, pharmacological inhibition of GSK3 by LiCl and SB-216763 increased cell proliferation across a range of postnatal ages. LiCl treatments also led to increased levels of beta-catenin and Snail and decreased expression of E-cadherin. Transfection with a dominant-negative GSK3 beta enhanced proliferation in these epithelia in a cell-autonomous manner, while overexpression of wild-type GSK3 beta markedly reduced it. The evidence from these measurements and experimental manipulations indicates that the balance of active and inactive forms of GSK3 helps to determine whether mammalian vestibular supporting cells will proliferate; permitting proliferation during early development when inactive GSK3 predominates and progressively inhibiting proliferation, and thereby limiting the capacity for hair cell regeneration as more GSK3 becomes active during the first week of postnatal maturation.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1932-8451
pubmed:author
pubmed:copyrightInfo
(Copyright) 2008 Wiley Periodicals, Inc.
pubmed:issnType
Print
pubmed:volume
68
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1059-75
pubmed:dateRevised
2011-11-2
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
The influence of glycogen synthase kinase 3 in limiting cell addition in the mammalian ear.
pubmed:affiliation
Department of Neuroscience, University of Virginia School of Medicine, Charlottesville, VA 22908, USA. zl5p@virginia.edu
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural