title: Proliferative responses to growth factors decline rapidly during postnatal maturation of mammalian hair cell epithelia.
abstract: 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.
authors.affiliation: Department of Neuroscience, University of Virginia, School of Medicine, HSC Box 801392, MR-4 Bldg., Rm 5150, Lane Road, Charlottesville, VA 22908, USA.
authors.forename: Rende
authors.initials: R
authors.lastname: Gu
authors.forename: Mireille
authors.initials: M
authors.lastname: Montcouquiol
authors.forename: Mark
authors.initials: M
authors.lastname: Marchionni
authors.forename: Jeffrey T
authors.initials: JT
authors.lastname: Corwin
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001973:Bromodeoxyuridine / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004848:Epithelium / Q000187:drug effects / Q000254:growth & development*; D005260:Female; D006198:Hair Cells, Auditory / Q000187:drug effects*; D007328:Insulin / Q000494:pharmacology; D008565:Membrane Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D020890:Neuregulin-1; D009924:Organ Culture Techniques; D010750:Phosphoproteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D062826:Zonula Occludens-1 Protein
chemical_list: D007328:Insulin; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D020890:Neuregulin-1; C490580:Nrg1 protein, rat; D010750:Phosphoproteins; C569042:TJP1 protein, human; C569044:Tjp1 protein, rat; D062826:Zonula Occludens-1 Protein; D001973:Bromodeoxyuridine