title: MicroRNA181a plays a key role in hair cell regeneration in the avian auditory epithelium.
abstract: Specialized sensory-transducing hair cells regenerate in response to injury in non-mammalian vertebrates such as birds and fish but not in mammals. Previous work has shown that overexpression of microRNA181a (miR181a) in cultured chicken basilar papillae, the avian counterpart of the cochlea, is sufficient to stimulate proliferation with production of new hair cells. The present study investigates the role of miR181a in hair cell regeneration after injury in explants of chicken auditory epithelia. Basilar papillae were explanted from 0-day-old chickens and transfected with either anti-miR181a, which knocks down endogenous miR181a, or a non-targeting miRNA and cultured with streptomycin to eliminate all hair cells from the epithelium. Labeling with BrdU was used to quantify proliferation. Explants exposed to streptomycin and transfected with anti-miR181a had significantly fewer BrdU positive cells than basilar papillae treated with streptomycin and transfected with a non-targeting miRNA. Activated caspase-3 and myosin VI labeling were used to show that the pattern of hair cell death and loss, respectively, were not affected by anti-miR181a transfection. MiR181a downregulation therefore seems to dimish the proliferative component of hair cell regeneration rather than prevent hair cell death following ototoxic injury.
authors.affiliation: Medical Scientist Training Program, Yale School of Medicine, 367 Cedar Street, Room 316 ESH, New Haven, CT 06522, USA. corey.frucht@yale.edu
authors.forename: Corey S
authors.initials: CS
authors.lastname: Frucht
authors.forename: Joseph
authors.initials: J
authors.lastname: Santos-Sacchi
authors.forename: Dhasakumar S
authors.initials: DS
authors.lastname: Navaratnam
mesh_terms: D000818:Animals; D002642:Chick Embryo; D002645:Chickens; D003051:Cochlea / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015536:Down-Regulation / Q000235:genetics; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics*; D006198:Hair Cells, Auditory / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D009416:Nerve Regeneration / Q000187:drug effects / Q000502:physiology*; D009498:Neurotoxins / Q000633:toxicity; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D009924:Organ Culture Techniques; D013307:Streptomycin / Q000633:toxicity
chemical_list: D035683:MicroRNAs; D009498:Neurotoxins; D016376:Oligonucleotides, Antisense; C529100:mirn181 microRNA, mouse; D013307:Streptomycin