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Dosing pregnant dams with alcohol (2\u00d7 2.9 g\/kg ethanol spaced 4 hr on day 8) induced FASD in B6J at a higher incidence than B6N embryos. Counter\u2010exposure to PK11195 (4 mg\/kg) significantly protected B6J embryos but slightly promoted FASD in B6N embryos. Microarray transcript profiling was performed on the embryonic headfold 3 hr after the first maternal alcohol injection (GEO data series accession GSE1074). This analysis revealed metabolic and cellular reprogramming that was substrain\u2010specific and\/or PK11195\u2010dependent. Mapping ethanol\u2010responsive KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways revealed down\u2010regulation of ribosomal proteins and proteasome, and up\u2010regulation of glycolysis and pentose phosphate pathway in B6N embryos; and significant up\u2010regulation of tight junction, focal adhesion, adherens junction, and regulation of the actin cytoskeleton (and near\u2010significant up\u2010regulation of Wnt signaling and apoptosis) pathways in both substrains. Expression networks constructed computationally from these altered genes identified entry points for EtOH at several hubs (MAPK1, ALDH3A2, CD14, PFKM, TNFRSF1A, RPS6, IGF1, EGFR, PTEN) and for PK11195 at AKT1. Our findings are consistent with the growing view that developmental exposure to alcohol alters common signaling pathways linking receptor activation to cytoskeletal reorganization. The programmatic shift in cell motility and metabolic capacity further implies cell signals and responses that are integrated by the mitochondrial recognition site for PK11195. Developmental Dynamics 236:613\u2013631, 2007. \u00a9 2007 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/dvdy.21048","type":"journal-article","created":{"date-parts":[[2007,1,3]],"date-time":"2007-01-03T15:12:55Z","timestamp":1167837175000},"page":"613-631","source":"Crossref","is-referenced-by-count":120,"title":["Reprogramming of genetic networks during initiation of the Fetal Alcohol Syndrome"],"prefix":"10.1002","volume":"236","author":[{"given":"Maia L.","family":"Green","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amar V.","family":"Singh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yihzi","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly A.","family":"Nemeth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen 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