An in-vivo model for hair cell regeneration in frog cristaampullaris.

Hair cells are the primary sensory receptors in both auditory and vestibular organs. In mammals hair cell proliferation and differentiation occur only during embryonic development. In lower vertebrates hair cell production occur at very low levels during adult life, but they retain the ability to regenerate the sensory epithelium after hair cell loss due to different agents such as aminoglycosides. We induced frog crista ampullaris degeneration by intraotic gentamicin administration. Drug induced degeneration starts within 24-48 hrs post treatment and proceeds to be maximal at day 4-5; regeneration is evident at day 6-7 and is almost complete at day 10-11. During degeneration we can first detect the loss of hair cell bundles. Later on we observe two different ways of hair cell degeneration: in some cells we can see vacuolization, nuclear and cytoplasmic swelling followed by enucleation and complete cell degeneration. In other cells morphological data suggest an apoptotic pathway. The degeneration process seems to start in the intermediate zone of the crista ampullaris and then proceeds in the central and lateral regions leaving holes all over the sensory epithelium. These apparent non homogeneous sensitivity to drug induced degeneration seems to correlate with morphofunctional differences of hair cells located in the intermediate, central and lateral compartments of the crista ampullaris. Regeneration starts while degeneration is still occurring and leads to the complete restoration of the sensory epithelium. During the regeneration process we can see supporting cells located nearby the sites of hair cell degeneration, assuming some hair cell-like characteristics as more developed endoplasmic reticulum and Golgi apparatus and immature kinocilia. At the same time, we can see undifferentiated cells spanning the entire epithelium from the basal region to the lumen, with a nuclear morphology similar to those of supporting cells.