The Role of the MAPK Pathway in Drosophila during Developmental Ethanol Exposure

Drosophila females lay eggs in rotting fruit, resulting in larval exposure to high concentrations of ethanol. These ethanol concentrations are toxic, leading to significant lethality and developmental delays. Our previous work demonstrates that these phenotypes are partially mediated by the insulin receptor. The insulin receptor can activate several pathways, including the Ras/Mitogen Activated Protein Kinase (MAPK) pathway, which is important in cell growth, differentiation, and proliferation. Unpublished data from our lab indicates that increasing activity of this pathway is protective against the toxic effects of ethanol. The goal of this project is to further investigate the role of the MAPK pathway in the developmental response to ethanol.  We predict that increasing MAPK pathway activity will result in protection, while reduced activity will lead to ethanol sensitivity. As predicted, ubiquitous expression of an RNA interference (RNAi) construct targeting vacuolar peduncles (vap), a negative regulator of the pathway, resulted in a significant increase in survival of flies reared in 6% ethanol. In addition, a loss of function mutation in dsor, which encodes MAP Kinase Kinase (MAPKK), which is required for the activation of MAPK, caused a significant increase in ethanol-induced developmental delay compared with control flies. These results show that the MAPK pathway is a target of ethanol exposure during Drosophila development. Future work will include determining the critical period for ethanol induced delay in the dsor mutant.