Correcting developmental errors by apoptosis: lessons from Drosophila JNK signaling.

Spatio-temporal regulation of the cell death machinery is essential for normal development and homeostasis of multicellular organisms. While the molecular basis for the central cell death machinery driven by caspases is now well documented, its regulatory mechanisms, especially in the context of living animals, remain to be clarified. The c-Jun N-terminal kinase (JNK) pathway is an evolutionarily conserved kinase cascade that regulates the apoptotic machinery. In mammals, JNK signaling has been implicated in stress-induced apoptosis. Drosophila genetics has now provided evidence of a novel role for JNK-mediated cell death signaling in eliminating developmentally aberrant cells from a tissue. The JNK-dependent cell-elimination system is orchestrated by cell-cell communication between normal and aberrant cells and is essential for ensuring developmental robustness, as well as for protecting organisms against fatal abnormalities such as neoplastic development. These processes are mediated by cell competition, morphogenetic apoptosis, and intrinsic tumor suppression. A combinatorial approach using both genetic and live-imaging systems in Drosophila will be extremely powerful to decipher how JNK-mediated apoptosis works within multicellular communities.