s1. These altered genes suggest potential mechanisms for the abnormal development in FASD. However, novel the wide ranging developmental abnormalities in FASD are likely a consequence of the interaction of multiple genes. Examination of global gene expression provides a holistic view of genes that potentially interact and colla boratively contribute to the abnormal development. Alcohol exposure Inhibitors,Modulators,Libraries induced changes in a group of cellular adhesion genes in neuroblas toma cells. A brief ethanol exposure at gesta tion day 8 in mouse embryos altered expression of genes of metabolic, cell programming and cytoskeletal signaling pathways. An earlier alcohol exposure at E6 E8 also altered a set of genes related to PLUNC, neurofilament, and pale ear.
In animal models of prenatal alcohol exposure, sources of variability include the pattern, concentration, amount, and developmental stage of alcohol exposure, maternal stress, embryonic growth and maturation of embryos between litters and even within a given litter and within inbred Inhibitors,Modulators,Libraries strains of mice. Control of all these variables in rapidly developing embryos is virtually unattainable in vivo. To limit these variables, a whole embryonic culture was adopted, including stage alignment based on somite number, in which the pat tern, amount and concentration of alcohol and embryo nic staging were controlled. Inbred C57BL 6 mice, with known susceptibility to ethanol teratogenesis, were used for this study. Differences in the dose and timing of alcohol exposure are known contributors to variation in the phenotypic spectrum in FASD.
Understanding the pattern of gene alterations that co vary with different outcomes pro duced by different alcohol doses or developmental tim ing of exposure would provide valuable insights into mechanisms underlying this phenotypic variability. As development is highly dynamic throughout gestation, we asked how alcohol exposure Inhibitors,Modulators,Libraries might affect genome wide gene expression at the critical stage Inhibitors,Modulators,Libraries of neurulation, when the nervous system are actively forming in mouse. We have shown that at this key stage, neural tube formation was highly sensi tive to Drug_discovery the alcohol insult. DNA methylation was altered, with the degree of change commensurate with severity of neural tube defect.
In the current study, in an initial experiment, cluster analysis indicated dis tinct differences in gene expression not only between control and alcohol treated embryos, but also between two phenotypic subsets of alcohol treated embryos dis cernable at the end of alcohol treatment, one group tech support which had a closed neural tube and the other group with an open neural tube. A second study with a larger set of arrays was then per formed in which alcohol treated embryos of both neural tube phenotypes were specifically compared. We report here the correlation of alcohol induced embryonic growth retardation and neural tube abnormalities with changes in expression in networks of genes known to regulate embryonic growth, organ development, and neural