Proliferative responses to growth factors decline rapidly during postnatal maturation of mammalian hair cell epithelia

Rende Gu, Mireille Montcouquiol, Mark Marchionni, Jeffrey T. Corwin
European Journal of Neuroscience. 2007-04-05; 25(5): 1363-1372
DOI: 10.1111/j.1460-9568.2007.05414.x

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1. Eur J Neurosci. 2007 Mar;25(5):1363-72.

Proliferative responses to growth factors decline rapidly during postnatal
maturation of mammalian hair cell epithelia.

Gu R(1), Montcouquiol M, Marchionni M, Corwin JT.

Author information:
(1)Department of Neuroscience, University of Virginia, School of Medicine, HSC
Box 801392, MR-4 Bldg., Rm 5150, Lane Road, Charlottesville, VA 22908, USA.

Millions of lives are affected by hearing and balance deficits that arise as a
consequence of sensory hair cell loss. Those deficits affect mammals permanently,
but hearing and balance recover in nonmammals after epithelial supporting cells
divide and produce replacement hair cells. Hair cells are not effectively
replaced in mammals, but balance epithelia cultured from the ears of rodents and
adult humans can respond to hair cell loss with low levels of supporting cell
proliferation. We have sought to stimulate vestibular proliferation; and we
report here that treatment with glial growth factor 2 (rhGGF2) yields a 20-fold
increase in cell proliferation within sheets of pure utricular hair cell
epithelium explanted from adult rats into long-term culture. In epithelia from
neonates, substantially greater proliferation responses are evoked by rhGGF2
alone, insulin alone and to a lesser degree by serum even during short-term
cultures, but all these responses progressively decline during the first 2 weeks
of postnatal maturation. Thus, sheets of utricular epithelium from newborn rats
average > 40% labelling when cultured for 72 h with bromo-deoxyuridine (BrdU) and
either rhGGF2 or insulin. Those from 5- and 6-day-olds average 8-15%, 12-day-olds
average < 1% and after 72 h there is little or no labelling in epithelia from 27-
and 35-day-olds. These cells are the mammalian counterparts of the progenitors
that produce replacement hair cells in nonmammals, so the postnatal quiescence
described here is likely to be responsible for at least part of the mammalian
ear's unique vulnerability to permanent sensory deficits.

DOI: 10.1111/j.1460-9568.2007.05414.x
PMID: 17425563 [Indexed for MEDLINE]


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