DESCRIPTION: This research focuses on hair cell regeneration in the inner ear of birds and mammals. Past research has shown that birds have the capacity to regenerate a nearly normal number and pattern of hair cells in the cochlea and vestibular epithelia after otologic trauma. These regenerated hair cells are functional, establish connections with the brain and restore behavioral losses. Mammals show very limited proliferation and no hair cell differentiation and remain hearing- or balance-impaired after similar trauma. This continuation of this research program will attempt to better understand the biological mechanisms underlying this regeneration process in birds by intensive study of the hair cell progenitors in avian and mammalian inner ear tissue. Three approaches to these problems are proposed. One set of experiments will use three-dimensional electron microscopic reconstructions of normal and regenerating sensory epithelium from the cochlea of chicks to examine the variations of sensory epithelium supporting cell morphology and ultrastructure in normal animals as regeneration begins. A second set of experiments will attempt to isolate the hair cell progenitors from the avian cochlea by making culture systems enriched for mitotic cells and then isolating this population into a purified group of regenerative supporting cells. The third group of experiments will use a novel co-culture system to examine the roles of diffusible factors in the regulation of sensory epithelium supporting cell mitotic activity in birds and mammals.