Activin potentiates proliferation in mature avian auditory sensory epithelium.
Humans and other mammals are highly susceptible to permanent hearing and balance deficits due to an inability to regenerate sensory hair cells lost to inner ear trauma. In contrast, nonmammalian vertebrates, such as birds, robustly regenerate replacement hair cells and restore hearing and balance functions to near-normal levels. There is considerable interest in understanding the cellular mechanisms responsible for this difference in regenerative capacity. Here we report on involvement of the TGFbeta superfamily type II activin receptors, Acvr2a and Acvr2b, in regulating proliferation in mature avian auditory sensory epithelium. Cultured, posthatch avian auditory sensory epithelium treated with Acvr2a and Acvr2b inhibitors shows decreased proliferation of support cells, the cell type that gives rise to new hair cells. Conversely, addition of activin A, an Acvr2a/b ligand, potentiates support cell proliferation. Neither treatment (inhibitor or ligand) affected hair cell survival, suggesting a specific effect of Acvr2a/b signaling on support cell mitogenicity. Using immunocytochemistry, Acvr2a, Acvr2b, and downstream Smad effector proteins were differentially localized in avian and mammalian auditory sensory epithelia. Collectively, these data suggest that signaling through Acvr2a/b promotes support cell proliferation in mature avian auditory sensory epithelium and that this signaling pathway may be incomplete, or actively blocked, in the adult mammalian ear.
McCullar
Jennifer S
JS
Department of Otolaryngology-Head and Neck Surgery, Virginia Merrill Bloedel Hearing Research Center, University of Washington, Seattle, Washington 98195-7923, USA.
Ty
Sidya
S
Campbell
Sean
S
Oesterle
Elizabeth C
EC
D030301:Activin Receptors, Type II / Q000378:metabolism; D028341:Activins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D001973:Bromodeoxyuridine / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D049109:Cell Proliferation / Q000187:drug effects*; D002642:Chick Embryo; D002645:Chickens; D003053:Cochlear Duct / Q000166:cytology*; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D004848:Epithelium / Q000033:anatomy & histology / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology*; D006198:Hair Cells, Auditory / Q000166:cytology / Q000378:metabolism; D007760:Labyrinth Supporting Cells / Q000378:metabolism; D051379:Mice; D009924:Organ Culture Techniques; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D051785:Smad Proteins / Q000378:metabolism
D055748:SOXB1 Transcription Factors; D051785:Smad Proteins; D028341:Activins; D030301:Activin Receptors, Type II; C425585:activin receptor type II-A; C425584:activin receptor type II-B; D001973:Bromodeoxyuridine