Stanley, NJ; (2013) Integrin Expression in the Mouse Vestibular System. Doctoral thesis , UCL (University College London).

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Abstract

The mammalian utricle has shown limited capacity for spontaneous regeneration of hair cells within a damaged sensory epithelium. In vivo and in vitro exposure of the tissue to ototoxic aminoglycosides has been utilised to induce hair cell loss, in order to study these regenerative events. The mammalian utricle is believed to regenerate hair cells by the direct transdifferentiation of supporting cells without a mitotic event. The cellular and molecular mechanisms behind this regenerative capability continue to be the subject of inner ear research. The integrin family of cell surface receptors are known for their key role in cellular adhesion, both to the extracellular matrix and to neighbouring cells. Studies of integrins have shown that they are also involved in numerous cellular processes including proliferation, differentiation and migration. They are therefore a likely candidate for involvement in the cellular events which underlie the regenerative ability demonstrated by the mammalian utricle. This study has identified a subset of the mammalian integrin subunits as being present in the normal adult mouse utricle. The identification of these integrins was achieved by both degenerate PCR and qPCR screening of utricular cDNA. Through immunohistochemistry, β1 and α6 have been shown to localise at the basement membrane of normal utricular tissue. Integrins β3 and β5 appear to be expressed within vestibular hair cells. Integrins β1, αV, β5, β3 and α6 are also present within the mesenchyme. The utricular macula of adult mice was utilised as an in vitro model in order to induce hair cell loss by gentamicin treatment and investigate integrin expression in the utricle during this process and subsequent regeneration. Relative quantification of qPCR data has indicated that a number of integrins including β1, αV and β3 show an increase in expression level at 4 days post treatment. Immunohistochemistry shows some changes in integrin localisation between 4 and 21 days post-gentamicin.

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