Effect of Nicotine on neural tube development

Neural tube defects (NTD) occur in 3000 births per year in the US. Several risk factors have been proposed for NTDs including both first hand and passive smoking during the periconceptual period. Previously we reported an increased frequency of cervical region NTD in a chicken model of prenatal nicotine exposure (Bohn, Humphrey et al. 2014; Humprey, Bohn et al. 2014). Here, we will reveal the mechanisms of the insult. The specific aims include: 1) Evaluation of the gene expression changes in the chicken model of nicotine exposure that we developed previosly. Such genome-wide analysis of the expression allows to collect very detailed data regarding the drug impact. To our knowlidge, comparable analysis of nicotine induced changes in gene expression during development of any species has never been conducted. 2) Evaluation of nicotine induced alterations in tadpoles (Xenopus tropica). The frogs will be treated in a manner similar to chicken (the same drug doses and a matched time of sacrifice) and analyzed both histologically and for gene expression. Incorporation of a different group of vertebrates in this study is essential for dissecting the evolutionary conserved role this pathway of interest in development which is another strong aspect of this proposal. We believe, that our comparative approach will allow more effective extrapolation of data from animal models to humans and better understanding of the evolutionary process. Nicotine is one of the most common developmental insults in humans. The consequences of this exposure are well-documented. However, the affected pathways are unknown. The identification of the mechanisms of nicotine induced alterations proposed here is vital for development of better treatment strategies. Overall design: There are 2 variables, Nicotine treatment (Nicotine treated and control) and days of incubation (5 days and 7 days). For each treatment 4 biological replicates were used.