Rab11 negatively regulates Wingless preventing JNK mediated apoptosis inDrosophilaepithelium during embryonic dorsal closure

Cell signaling pathways involved in epithelial wound healing, show a lot of complexities when it comes to their regulation. Remarkably, a large proportion of these signaling pathways are triggered at the time of morphogenetic events which usually involve epithelial sheet fusions during embryonic development, such as the event of dorsal cloure in Drosophila embryos. One such conserved pathway in the wound healing process is the JNK-Dpp signaling pathway. Recent observations suggest that one such upstream regulator of JNK mediated apoptosis could be Rab11, a small Ras like GTPase, which is functionally associated with the membrane and cortical cytoskeletal organization of epithelial cells. Using Drosophila embryonic dorsal closure as a model of wound healing, we observed that a targeted expression of a Rab11 loss of function mutant in the dorso-lateral epidermis of fly embryos (tissue which extends contra-laterally in order to fill the intervening gap) undergoing dorsal closure leads to an ectopic expression of Caspase-3 and a concomitant up-regulation of the JNK-Dpp signaling. This resulted in the death of the dorso-lateral epithelial cells with a consequent embryonic lethality due to dorsal closure defects. Interestingly, a simultaneous knockdown of wingless (another developmentally conserved gene) in Rab11 mutants resulted in a rescue of the lethal phenotype and also a significant level of successful completion of the dorsal closure process. In our experiments we suggest Rab11 could promote cross talk between the JNK-Dpp pathway and the canonical wingless pathway in the regulation of apoptosis in the dorsolateral epithelium of fly embryos undergoing dorsal closure. One Sentence Summary Rab11 functions through a conserved Wingless mediated JNK-Dpp pathway during embryonic dorsal closure.