spla1, a phospholipase A2 gene, is essential for oogenesis in Drosophila melanogaster

Phospholipid metabolism generates bioactive lipids, which act as second messengers for a variety of signal transduction pathways. Although much has been learned by biochemical and pharmacological studies, functional analysis of phospholipid metabolism has been complicated for the following reasons. First, most phospholipid metabolites have signaling functions and can be further metabolized to other bioactive lipids by numerous enzymes. This has made it difficult to determine which molecule acts as the second messenger in many systems. In addition, an organism often expresses multiple genes that encode the same class of enzyme. This has often made it difficult to attribute function to individual isozymes.;A genetic approach provides a potential solution to these problems. Removal of a gene will determine the essential function of an individual isozyme. Once a mutation has been characterized, a screen for genetic interactors will allow one to deduce which bioactive lipid is responsible for a given function. However, relatively few genetic models have been developed to date for the functional analysis of phospholipid metabolism. This thesis presents a genetic dissection of spla1 (secreted phospholipase A2- 1) in Drosophila melanogaster. Loss of spla1 function causes female sterility. Closer examination of mutants revealed numerous defects, including apoptosis and disrupted follicle cell migration in developing egg chambers, and abnormal eggshell morphology in the few eggs that were laid. Unlinked noncomplementation of these phenotypes was observed in females transheterozygous for mutations in spla1 and Cct1, a gene believed to be involved in synthesizing substrate for phospholipase A2s. Taken together, our data suggests that Spla1 enzymatic activity is essential for cell migratory events and egg chamber survival during oogenesis. These results should provide a solid foothold for further study of the role of phospholipid metabolism in the female reproductive system.