Understanding prosensory specification for improved regenerative therapies in the inner ear

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Our senses of hearing and balance depend on specialized 'hair' cells located in the sensory organs of the inner ear. The hair cells are only produced during the embryonic development of the inner ear, and their disappearance in adult life is the leading cause of hearing loss, in particular in the ageing population. The treatments for hearing loss are limited to hearing aids or cochlear implants, and there is considerable need and pressure for new and more efficient therapies. One possible cure could be to induce hair cell regeneration in the damaged inner ear - a process that is naturally occurring in non-mammalian vertebrates. The current approaches to achieve this rely on the artificial re-activation of 'pro-hair cell' signals, responsible for the induction of hair cell formation during embryonic development. However, growing evidence indicate that the cells of the adult cochlea cannot easily convert into hair cells when exposed to those signals. An alternative strategy might be to turn cells of the adult inner ear into 'prosensory' cells, which during normal development are the parent cells giving rise to both hair cells and their associated 'supporting' cells. A first step towards this goal is to understand how these prosensory cells are formed during normal development. Using DNA-Sequencing and bioinformatics methods, we have already identified a number of genes and signals that could be potentially be important for the formation of prosensory cells. The aims of this project are to test their functions, by artificially modifying their expression or activity during the development of the embryonic chicken inner ear. The results of this project will help us to pinpoint the specific genes and cell-to-cell communication systems that could be manipulated to trigger hair cell regeneration in the damaged inner ear. In the future, this research could open up new venues for more efficient therapies for hearing loss in humans.