Mitogenic signaling from apoptotic cells in Drosophila

Apoptotic cells of Drosophila not only activate caspases, but also are able to secrete developmental signals like Hedgehog (Hh), Decapentaplegic (Dpp) and Wingless (Wg) before dying. Since Dpp and Wg are secreted in growing tissues and behave as growth factors, it was proposed that they play a role in compensatory proliferation, the process by which a growing blastema can restore normal size after massive apoptosis. We discuss recent results showing that there is normal compensatory proliferation in the absence of Dpp/Wg signaling, thus indicating it has no significant role in the process. Furthermore, we argue that Dpp/Wg signaling is not a resident feature of apoptotic cells, but a side effect of the necessary activation of the JNK pathway. Nevertheless, the ectopic JNK/Dpp/Wg signaling may have an important role in tissue regeneration. Recent work in other organisms suggests that paracrine signaling from apoptotic cells may be of general significance in wound healing and tissue regeneration in metazoans.