Roles of sphingolipids in Drosophila development and disease

Abstract

The last 10 years have seen a rebirth of interest in lipid biology in the fields of Drosophila development and neurobiology, and sphingolipids have emerged as controlling many processes that have not previously been studied from the viewpoint of lipid biochemistry. Mutations in sphingolipid regulatory enzymes have been pinpointed as affecting cell survival and growth in tissues ranging from muscle to retina. Specification of cell types are also influenced by sphingolipid regulatory pathways, as genetic interactions of glycosphingolipid biosynthetic enzymes with many well-known signaling receptors such as Notch and epidermal growth factor receptor reveal. Furthermore, studies in flies are now uncovering unexpected roles of sphingolipids in controlling lipid storage and response to nutrient availability. The sophisticated genetics of Drosophila is particularly well suited to uncover the roles of sphingolipid regulatory enzymes in development and metabolism, especially in light of conserved pathways that are present in both flies and mammals. The challenges that remain in the field of sphingolipid biology in Drosophila are to combine traditional developmental genetics with more analytical biochemical and biophysical methods, to quantify and localize the responses of these lipids to genetic and metabolic perturbations.