One of the major causes of birth defects in North America is maternal ethanol consumption. Maternal alcohol consumption during critical windows of embryonic development can result in offspring with a number of predictable defects known as Fetal Alcohol Syndrome (FAS) and Fetal Alcohol Effects (FAE). The effects of ethanol on normal development is very costly to society since FAS and FAE children suffer from impaired development, cognitive deficits and behavior problems. In order to reduce the cost of the devastating effects of ethanol on human health, we must understand the mechanism of ethanol action. It is also essential that we determine the genetic factors involved. A greater understanding of underlying mechanisms) of ethanol action on developing embryos should lead to new ideas about prevention and intervention of FAS and FAE. Although several hypotheses have been proposed to explain the molecular mechanism of ethanol-mediated fetal injury, the cause remains uncertain. The long-range goal of this project is to establish zebrafish as a vertebrate model to understand the molecular mechanisms) of ethanol-induced fetal injury. Zebrafish embryos share many cellular, anatomical, and physiological characteristics with higher vertebrates including humans and they offer many practical advantages making them an excellent research model for teratogenic studies. We specifically propose to: (I) Investigate the potential involvement of ethanol metabolism by completely characterizing the metabolizing pathways in developing embryos. (II) Determine the critical developmental window for embryonic CNS injury. (III) Identify the impact of ethanol exposure on zebrafish nervous system development and test the hypothesis that cell death contributes significantly to the teratogenic actions of ethanol. Completion of this project will result in a powerful model system that will allow for a greater understanding of the molecular mechanisms underlying ethanol-mediated fetal injury.
