Bird, J.E.; (2007) Wound repair in sensory organs of the avian inner ear. Doctoral thesis , University of London.

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Abstract

Hair cells are the sensory receptors of the inner ear, converting sound and accelerations into neuronal signals. Unlike mammals, birds are able to regenerate their sensory function after auditory or vestibular trauma. Sensory regeneration requires a composite programme of epithelial repair, hair cell production and functional reinnervation. The purpose of this thesis was to explore the mechanisms of epithelial repair in the avian inner ear, and examine their contribution within the broader process of sensory regeneration. An epithelial cell culture model of the chick utricle (Gallus gallus) was developed to facilitate in vitro experimentation. Initial investigations utilised laser ablation to create wounds in the sensory epithelium. Epithelial wounds were found to heal within 4 hours using a contractile acto-myosin cable in combination with lamellipodia driven cell crawling. Nuclear incorporation of BrdU was also used to assess support cell proliferation at the sites of epithelial wounds. Proliferation was significantly increased within 48 hours of laser ablation, and was spatially restricted to the areas of epithelial trauma. The increase was strongly reduced by pharmacological blockade of PI3K, but only partially so using inhibitors of the ERK and JNK MAP kinases. The response of the avian sensory epithelium to aminoglycoside ototoxicity has also been investigated. Streptomycin sulphate was used to induce extensive hair cell death in explant cultures of the chick utricle. During this process, support cells were found to remodel and eliminate the hair cell from the epithelial surface. Time-lapse microscopy of p-actin-EGFP revealed that support cells formed a cable of f-actin around the hair cell neck. The cable subsequently constricted to repair the epithelial defect, and in doing so severed and ejected the hair bundle. Support cells adjacent to a dying hair cell also extended pseudopodia basolaterally to form a distinctive calyx of f- actin around the soma. Simultaneous time-lapse recordings of p-actin-EGFP with TOTO-3 revealed that the support cell calyx was a phagocytic structure, which culminated in the engulfment of the hair cell. These results demonstrated that support cells have a proactive role in both maintenance of epithelial integrity and the removal of corpses during hair cell death.

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