title: Reinforcement of cell junctions correlates with the absence of hair cell regeneration in mammals and its occurrence in birds.
abstract: Debilitating hearing and balance deficits often arise through damage to the inner ear's hair cells. For humans and other mammals, such deficits are permanent, but nonmammalian vertebrates can quickly recover hearing and balance through their innate capacity to regenerate hair cells. The biological basis for this difference has remained unknown, but recent investigations in wounded balance epithelia have shown that proliferation follows cellular spreading at sites of injury. As mammalian ears mature during the first weeks after birth, the capacity for spreading and proliferation declines sharply. In seeking the basis for those declines, we investigated the circumferential bands of F-actin that bracket the apical junctions between supporting cells in the gravity-sensitive utricle. We found that those bands grow much thicker as mice and humans mature postnatally, whereas their counterparts in chickens remain thin from hatching through adulthood. When we cultured utricular epithelia from chickens, we found that cellular spreading and proliferation both continued at high levels, even in the epithelia from adults. In contrast, the substantial reinforcement of the circumferential F-actin bands in mammals coincides with the steep declines in cell spreading and production established in earlier experiments. We propose that the presence of thin F-actin bands at the junctions between avian supporting cells may contribute to the lifelong persistence of their capacity for shape change, cell proliferation, and hair cell replacement and that the postnatal reinforcement of the F-actin bands in maturing humans and other mammals may have an important role in limiting hair cell regeneration.
authors.affiliation: Department of Biomedical Engineering, University of Virginia School of Engineering and Applied Science, Charlottesville, Virginia 22908, USA. jcb7j@virginia.edu
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Burns
authors.forename: Joseph
authors.initials: J
authors.lastname: Burns
authors.forename: J Jared
authors.initials: JJ
authors.lastname: Christophel
authors.forename: Maria Sol
authors.initials: MS
authors.lastname: Collado
authors.forename: Christopher
authors.initials: C
authors.lastname: Magnus
authors.forename: Matthew
authors.initials: M
authors.lastname: Carfrae
authors.forename: Jeffrey T
authors.initials: JT
authors.lastname: Corwin
mesh_terms: D000199:Actins / Q000378:metabolism; D000375:Aging / Q000473:pathology / Q000502:physiology; D000818:Animals; D049109:Cell Proliferation; D048430:Cell Shape; D002645:Chickens; D004548:Elasticity; D004848:Epithelium / Q000033:anatomy & histology / Q000502:physiology; D005260:Female; D006198:Hair Cells, Auditory / Q000473:pathology / Q000502:physiology* / Q000648:ultrastructure; D018069:Hair Cells, Vestibular / Q000473:pathology / Q000502:physiology* / Q000648:ultrastructure; D006801:Humans; D007365:Intercellular Junctions / Q000378:metabolism* / Q000648:ultrastructure; D007760:Labyrinth Supporting Cells / Q000648:ultrastructure; D051379:Mice; D012038:Regeneration / Q000502:physiology*; D012444:Saccule and Utricle / Q000648:ultrastructure; D046509:Tissue Culture Techniques
chemical_list: D000199:Actins