In Vitro Differentiation of Inner Ear Hair Cells

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DESCRIPTION (provided by applicant): Sensorineural deafness in adults is primarily due to the permanent loss of sensory hair cells in the inner ear. In this regard, mammals differ from lower vertebrates, which can regenerate sensory hair cells from adjacent supporting cells after injury. It is not known whether this difference arises from a lack of sensory developmental capacity in mammalian support cells, or from a lack of some endogenous stimulus in mammals to provoke regeneration after otic injury. Experiments described in this proposal will mark embryonic sensory and support cell precursors with a fluorescent transgene. These precursors will be purified from embryos using fluorescence activated cell sorting (FACS) and differentiated in vitro, using a recently developed culture system. This system will also be used to isolate and differentiate post-mitotic support cells from embryos and from post-natal animals. From these experiments, it will be determined whether post-mitotic mammalian support cells are able to generate sensory hair cells, and if so, how long in development this capacity persists.