title: Eye-specific gene expression following embryonic ethanol exposure in zebrafish: roles for heat shock factor 1.
abstract: The mechanisms through which ethanol exposure results in developmental defects remain unclear. We used the zebrafish model to elucidate eye-specific mechanisms that underlie ethanol-mediated microphthalmia (reduced eye size), through time-series microarray analysis of gene expression within eyes of embryos exposed to 1.5% ethanol. 62 genes were differentially expressed (DE) in ethanol-treated as compared to control eyes sampled during retinal neurogenesis (24-48 h post-fertilization). The EDGE (extraction of differential gene expression) algorithm identified >3000 genes DE over developmental time in ethanol-exposed eyes as compared to controls. The DE lists included several genes indicating a mis-regulated cellular stress response due to ethanol exposure. Combined treatment with sub-threshold levels of ethanol and a morpholino targeting heat shock factor 1 mRNA resulted in microphthalmia, suggesting convergent molecular pathways. Thermal preconditioning partially prevented ethanol-mediated microphthalmia while maintaining Hsf-1 expression. These data suggest roles for reduced Hsf-1 in mediating microphthalmic effects of embryonic ethanol exposure.
authors.affiliation: Department of Biological Sciences, University of Idaho, Moscow, ID 83844, United States; Neuroscience Graduate Program, University of Idaho, Moscow, ID 83844, United States.
authors.forename: Bhavani
authors.initials: B
authors.lastname: Kashyap
authors.affiliation: Department of Biological Sciences, University of Idaho, Moscow, ID 83844, United States.
authors.forename: Laurel
authors.initials: L
authors.lastname: Pegorsch
authors.affiliation: Department of Biological Sciences, University of Idaho, Moscow, ID 83844, United States.
authors.forename: Ruth A
authors.initials: RA
authors.lastname: Frey
authors.affiliation: Department of Biological Sciences, University of Idaho, Moscow, ID 83844, United States; Neuroscience Graduate Program, University of Idaho, Moscow, ID 83844, United States.
authors.forename: Chi
authors.initials: C
authors.lastname: Sun
authors.affiliation: School of Molecular Biosciences, Washington State University, Pullman, WA 99164, United States; Center for Reproductive Biology, University of Idaho, Moscow, ID 83844, United States.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Shelden
authors.affiliation: Department of Biological Sciences, University of Idaho, Moscow, ID 83844, United States; Neuroscience Graduate Program, University of Idaho, Moscow, ID 83844, United States; Center for Reproductive Biology, University of Idaho, Moscow, ID 83844, United States. Electronic address: dstenkam@uidaho.edu.
authors.forename: Deborah L
authors.initials: DL
authors.lastname: Stenkamp
mesh_terms: D000818:Animals; D004625:Embryo, Nonmammalian / Q000187:drug effects / Q000378:metabolism; D000431:Ethanol / Q000633:toxicity*; D005123:Eye / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D000076249:Heat Shock Transcription Factors; D008850:Microphthalmos / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology; D029961:Zebrafish Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D000076249:Heat Shock Transcription Factors; D014157:Transcription Factors; D029961:Zebrafish Proteins; C411828:hsf1 protein, zebrafish; D000431:Ethanol
keywords: Ethanol; Eye; Fetal alcohol syndrome; Heat shock factor; Heat shock protein; Microarray; Retina; Zebrafish