Sphingolipids are complex membrane lipids, some of which, such as sphingosine-1-phosphate, act in signalling pathways that regulate cell death,survival, differentiation and migration in multicellular organisms. Herr et al. now report the identification and disruption, in Drosophila, of Sply, which encodes sphingosine-1-phosphate lyase, an enzyme that catalyses the catabolism of sphingosine-1-phosphate. Their findings, on , reveal, for the first time, that disrupted sphingolipid catabolism can directly cause complex developmental abnormalities in a metazoan. Sply-null mutants have abnormal dorsal longitudinal muscles (and so are flightless), reduced egg laying and larval viability, and accumulate sphingoid bases. These defects were rescued by restoring Sply expression and by introducing a suppressor mutation that reduces sphingolipid synthesis and the accumulation of sphingolipid intermediates. Such findings are a first step towards elucidating the roles of these signalling molecules in development and cell function.
