Functional assembly of mammalian cochlear hair cells |
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Authors: | Marcotti Walter |
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Affiliation: | Department of Biomedical Science, University of Sheffield, Sheffield S10 2TN, UK. w.marcotti@sheffield.ac.uk |
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Abstract: | Hair cells in the mammalian inner ear convert sound into electrical signals that are relayed to the nervous system by the chemical neurotransmitter glutamate. Electrical information encoding sound is then passed through the central nervous system to the higher auditory centres in the brain, where it is used to construct a temporally and spatially accurate representation of the auditory landscape. To achieve this, hair cells must encode fundamental properties of sound stimuli at extremely high rates, not only during mechano-electrical transduction, which occurs in the hair bundles at the cell apex, but also during electrochemical transduction at the specialized ribbon synapses at the cell base. How is the development of such a sophisticated cell regulated? More specifically, to what extent does physiological activity contribute to the progression of the intrinsic genetic programmes that drive cell differentiation? Hair cell differentiation takes about 3 weeks in most rodents, from terminal mitosis during embryonic development to the onset of hearing around 2 weeks after birth. Until recent years, most of the molecules involved in hair cell development and function were unknown, which was mainly due to difficulties in working with the mammalian cochlea and the very small number of hair cells, about 16,000 in humans, present in the auditory organ. Recent advances in the ability to record from the acutely isolated cochlea maintained in near-physiological conditions, combined with the use of genetically modified mouse models, has allowed the identification of several proteins and molecular mechanisms that are crucial for the maturation and function of hair cells. In this article, I highlight recent findings from my laboratory that have furthered our understanding of how developing hair cells acquire the remarkable sensitivity of adult auditory sensory receptors. |
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