The influence of glycogen synthase kinase 3 in limiting cell addition in the mammalian ear.

@article{citeulike:2856489, abstract = {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 GSK3beta decreases postnatally in the murine utricular epithelium, as E-cadherin and the active forms of GSK3alpha and GSK3beta 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 GSK3beta enhanced proliferation in these epithelia in a cell-autonomous manner, while overexpression of wild-type GSK3beta 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. (c) 2008 Wiley Periodicals, Inc. Develop Neurobiol, 2008.}, address = {Department of Neuroscience, University of Virginia School of Medicine, Charlottesville, Virginia 22908.}, author = {Lu, Zhenjie and Corwin, Jeffrey T T. }, citeulike-article-id = {2856489}, doi = {http://dx.doi.org/10.1002/dneu.20635}, issn = {1932-8451}, journal = {Developmental neurobiology}, keywords = {gsk3, snail}, month = {May}, posted-at = {2008-06-02 12:46:09}, priority = {2}, title = {The influence of glycogen synthase kinase 3 in limiting cell addition in the mammalian ear.}, url = {http://dx.doi.org/10.1002/dneu.20635}, year = {2008} }

TY - JOUR ID - citeulike:2856489 L3 - citeulike-article-id:2856489 TI - The influence of glycogen synthase kinase 3 in limiting cell addition in the mammalian ear. JF - Developmental neurobiology AD - Department of Neuroscience, University of Virginia School of Medicine, Charlottesville, Virginia 22908. SN - 1932-8451 N2 - 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 GSK3beta decreases postnatally in the murine utricular epithelium, as E-cadherin and the active forms of GSK3alpha and GSK3beta 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 GSK3beta enhanced proliferation in these epithelia in a cell-autonomous manner, while overexpression of wild-type GSK3beta 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. (c) 2008 Wiley Periodicals, Inc. Develop Neurobiol, 2008. KW - gsk3 KW - snail AU - Lu, Zhenjie AU - Corwin, Jeffrey T PY - 2008/05/09/ UR - http://dx.doi.org/10.1002/dneu.20635 ER -