Eye-specific gene expression following embryonic ethanol exposure in zebrafish: Roles for heat shock factor 1

• We examine eye-specific gene expression in zebrafish embryos exposed to EtOH.
• Components of the cellular stress response were differentially expressed.
• Sub-threshold EtOH plus sub-threshold hsf1 MO resulted in microphthalmia.
• Upregulation of the stress response partially rescued EtOH-induced microphthalmia.
• Reduced Hsf-1 may mediate the microphthalmic effects of EtOH.

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.