Abstracts - Speakers

First Annual Waggoner Center Advance - March 22, 2013

Johann Eberhart, PhD

Assistant Professor of Molecular Cell & Developmental Biology

What's Behind the Screen: Using Zebrafish to Identify and Characterize Ethanol-sensitive Genetic Loci

Maternal alcohol consumption can result in Fetal Alcohol Spectrum Disorders (FASD), a highly variable array of developmental defects often affecting the nervous system and craniofacial skeleton. The severity and extent of defects caused by fetal alcohol exposure is known to be mediated by numerous factors, including timing and concentration of alcohol. Genetic predisposition is also an important factor in FASD, yet we still understand little about the loci involved in this predisposition. The zebrafish is an ideal model organism in which to identify these loci because it is genetically tractable and produces large numbers of externally fertilized embryos, allowing for control over timing and dosage of ethanol. We have conducted two screens of zebrafish mutants to identify gene/ethanol interactions. In our initial screen of five zebrafish craniofacial mutants, we found that ethanol interacted strongly with platelet-derived growth factor receptor alpha (pdgfra). The pdgfra/ethanol interaction is synergistic and causes elevation in the levels of apoptosis in skeletal progenitor cells. In a larger follow up screen, we have examined 20 ethanol-treated zebrafish mutant lines for craniofacial and neural defects as well as elevated apoptosis. We have identified several novel gene/ethanol interactions, most of which generate distinct phenotypes, suggesting that genetics plays a role in FASD variation. Understanding this variation is important for the identification and potential treatment of FASD.