The role of Dpp and Wg in compensatory proliferation and in the formation of hyperplastic overgrowths caused by apoptotic cells in the Drosophila wing disc

Non-lethal stress treatments (X-radiation or heat shock) administered to Drosophila imaginal discs induce massive apoptosis, which may eliminate more that 50% of the cells. Yet the discs are able to recover to form final structures of normal size and pattern. Thus, the surviving cells have to undergo additional proliferation to compensate for the cell loss. The finding that apoptotic cells ectopically express dpp and wg suggested that ectopic Dpp/Wg signalling might be responsible for compensatory proliferation. We have tested this hypothesis by analysing the response to irradiation-induced apoptosis of disc compartments that are mutant for dpp, for wg, or for both. We find that there is compensatory proliferation in these compartments, indicating that the ectopic Dpp/Wg signalling generated by apoptotic cells is not involved. However, we demonstrate that this ectopic Dpp/Wg signalling is responsible for the hyperplastic overgrowths that appear when apoptotic ('undead') cells are kept alive with the caspase inhibitor P35. We also show that the ectopic Dpp/Wg signalling and the overgrowths caused by undead cells are due to a non-apoptotic function of the JNK pathway. We propose that the compensatory growth is simply a homeostatic response of wing compartments, which resume growth after massive cellular loss until they reach the final correct size. The ectopic Dpp/Wg signalling associated with apoptosis is inconsequential in compartments with normal apoptotic cells, which die soon after the stress event. In compartments containing undead cells, the adventitious Dpp/Wg signalling results in hyperplastic overgrowths.