Dpp signaling counteracts JNK-dependent apoptosis caused by epithelial disruption. Jorge V. Beira^1,2, Jean-Paul Vincent¹. 1) Developmental Biology Division, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, NW7 1AA, London, United Kingdom; 2) Research Department of Cell and Developmental Biology, University College London, Gower Street, London, United Kingdom.

   A dynamic balance between cell proliferation and cell death is crucial to maintain tissue homeostasis throughout embryonic development and adult life. Homeostatic apoptosis contributes to eliminate abnormal or defective cells, ensuring they do not spread uncontrollably. While the cellular machinery executing apoptosis has been relatively well characterized, our understanding of the upstream signals regulating homeostatic apoptosis is still fragmentary. For example, how the removal of apical determinants from the embryonic epidermis leads to apoptosis remains poorly understood. We have shown that JNK is a key mediator in this process: it is activated by epithelial disruption, as shown with a JNK sensor, and it itself leads to activation of reaper expression. Interestingly, JNK signaling does not trigger reaper expression throughout the epidermis. In the dorsal epidermis no reaper is expressed despite high level JNK signaling. We provide evidence that this could be because Dpp signaling, which is highly active in this region of the embryo, prevents rpr transcription. Our data suggest that a simple gene regulatory network integrating JNK- and Dpp-dependent inputs regulates reaper transcription and apoptosis. This network forms a bi-stable switch that enables JNK signaling to direct distinct outcomes, cell death or migratory activity, according to the local environment. The interplay between these conserved pathways and the apoptotic machinery could have implications for the elimination of pre-tumoral cells in vertebrates.