The EGFR/MAPK pathway is a target of developmental ethanol exposure in Drosophila.. Rachael L. French, Peter Luu, David Do, Nicole Delgado. Biological Sciences, San Jose State University, San Jose, CA.

   Alcohol exposure during development causes a variety of abnormalities in a broad range of taxa, from mammals to insects. In humans, prenatal alcohol exposure leads to an array of complications, from growth deficiency and birth defects to mental retardation and behavioral abnormalities, collectively described as fetal alcohol spectrum disorder (FASD) or fetal alcohol syndrome (FAS).
   Using our previously established fly model of FASD, we have found that at least some of ethanols deleterious effects can be modulated by mutation of genes in the Epidermal Growth Factor Receptor (EGFR) signal transduction pathway. In addition, we have found that ethanol exposure during development can reverse the lethality associated with ubiquitous overexpression of the EGFR pathway, demonstrating that ethanol exposure reduces signaling through this pathway during development. Finally, we have preliminary data indicating that flies reared in ethanol do not develop normal preference for ethanol-containing food as adults, and that this response is further blunted by mutation of dsor, the Drosophila homolog of MAP Kinase Kinase (MAPKK). These data indicate that the EGFR pathway is a target of ethanol exposure during development.
   We will present the above data, including analysis of the expression and activity of the EGFR pathway and MAP Kinase (MAPK) in ethanol-exposed larvae and microarray results indicating that genes in at least two MAPK pathways, the EGFR pathway and the Jun Kinase (JNK) pathway, are downregulated as a result of developmental ethanol exposure. Future research will focus on understanding how ethanol-induced changes in EGFR signaling lead to changes in growth and behavior and identification of neuronal targets of ethanol during neurobehavioral development.