p53 and Bax: putative death factors in taste cell turnover.
The turnover of cells in renewing epithelia presents an opportunity to examine cell death pathways in adult vertebrates. In mouse lingual epithelium a typical taste receptor cell survives for 9 days, until it is killed by an unknown cascade of death factors. Apoptosis was implicated by the presence of fragmented DNA in about 8% of taste receptor cells in the vallate papilla. In using immunocytochemistry to seek putative death factors, we observed that squamous epithelial cells of the tongue were negative for Bax, a death factor in the Bcl-2 family of survival/death factors, and were also negative for p53, a tumor-suppressor protein linked to apoptosis and Bax transcription. In contrast, 8-10% of the taste receptor cells were Bax-positive, and 9-11% were p53 positive. These immunopositive taste receptor cells were more likely to display death-related morphologic defects than other receptor cells, and they frequently coexpressed p53 and Bax. In both neonatal and adult mice, the labeling of dividing cells with 5-bromo-2'-deoxyuridine indicated that all Bax-positive taste cells were at least 5 days old. On postnatal day 7, when few taste cells were old, no more than 1% of taste cells were immunopositive for either p53 or Bax. We inferred that old taste receptor cells employ p53 and Bax as part of their apoptotic death pathway. The routine expression of p53 by postmitotic, aged taste cells broadens the conventional view that p53 is restricted to mitotic cells that have stress-damaged DNA. Furthermore, the scattered distribution of aged receptor cells within the taste bud excludes some explanations for stable taste signals during receptor cell turnover.