Destruction of hair cells in the human ear results in irreversible loss of equilibrium or hearing sensitivity since our ears do not produce hair cells after birth. Recently I demonstrated hair cell production occurring perpetually in the ears of sharks, skates, and amphibians. In some species this results in new cells equal to more than 50 times the number in the human cochlea and a 500-fold increase in physiological sensitivity. Neurons here also grow continually expanding their arbors to innervate new hair cells, and the populations of supporting cells in these epithelia turnover rapidly as demonstrated by labeling of DNA. In these ears, due to the persistence of hair cell production, the effects of hair cell damage may be reversible through regeneration. Here a plan is presented to continue investigating persistent sensory epithelium growth, to evaluate the regenerative capabilities of perpetually growing ears, and to test hypotheses concerning mechanisms that may control growth in hair cell sensory epithelia. The ultrastructure of the hair cell precursors in persistent germinative zones will be investigated by transmission electron microscopy. Aminoglycoside antibiotics and cryogenic surgery will be used to damage hair cells, then scanning electron microscopy will be used to evaluate the ear's ability to generate new hair cells in toads that normally continue to produce these cells. Rates of supporting cell turnover will be measured in the ears of adult toads and in the vestibular epithelia of mice through autoradiography. The regeneration of the processes of peripheral statoacoustic neurons and their guidance will be studied by denervating epithelia and in neuronal cell cultures. Experimental surgery in salamanders and transplantation of altered embryonic chick otocysts into host embyros and into organ culture will be used to examine trophic and inductive interactions between neurons and hair cells. The characteristics of growing hair cell epithelia are common to many forms including the embryonic ears of birds and mammals and the perpetually growing ears of anamniotes. The information sought here is essential for understanding the limits and capacities of regeneration and self repair in hair cell epithelia. It pertains directly to possible recovery from sensorineural hearing loss and balance disorders and to the development of normal and abnormal function in human ears.
