The role of the PI3K pathway in mediating Drosophila developmental ethanol effects

Fetal Alcohol Syndrome (FAS) is a spectrum disorder affecting individuals exposed to ethanol during gestation and results in growth and development defects, behavioral changes, and altered adult responses to ethanol.  We have previously demonstrated that Drosophila melanogaster larvae reared in ethanol-containing food display many of the same phenotypes.  We have also shown that upregulation of insulin during development rescues many of these ethanol-induced phenotypes. The purpose of this study is to determine whether downstream components of the phosphoinositide 3-kinase (PI3K) pathway are mediating these phenotypes. 

            Flies reared in 5-7% ethanol show reduced survival (approximately 50% of control survival). If the PI3K pathway is involved in mediating ethanol-induced phenotypes, then decreased pathway activity will amplify this effect, while increased activity should result in increased survival relative to wildtype flies.  We therefore generated flies with altered levels of PI3K signaling and tested these flies for survival in ethanol-containing food. We have found that altering expression of three genes in this pathway (Akt, Pdk and foxo) results in changes in survival in ethanol-containing food. We conclude that the PI3K pathway is involved in mediating the insulin-dependent mortality associated with developmental ethanol exposure.  Future work will include investigating the effects of the PI3K pathway on other ethanol-induced phenotypes (primarily ethanol-induced behavioral changes).