Ethanol Effects on Early Developmental Stages Studied Using the Zebrafish

Abstract

Fetal alcohol spectrum disorder (FASD) results from prenatal ethanol exposure. The zebrafish (Danio rerio) is an outstanding in vivo FASD model. Early development produced the three germ layers and embryonic axes patterning. A critical pluripotency transcriptional gene circuit of sox2, pou5f1 (oct4; recently renamed pou5f3), and nanog maintain potency and self-renewal. Ethanol affects sox2 expression, which functions with pou5f1 to control target gene transcription. Various genes, like elf3, may interact and regulate sox2, and elf3 knockdown affects early development. Downstream of the pluripotency transcriptional circuit, developmental signaling activities regulate morphogenetic cell movements and lineage specification. These activities are also affected by ethanol exposure. Hedgehog signaling is a critical developmental signaling pathway that controls numerous developmental events, including neural axis specification. Sonic hedgehog activities are affected by embryonic ethanol exposure. Activation of sonic hedgehog expression is controlled by TGF-ß family members, Nodal and Bmp, during dorsoventral (DV) embryonic axis establishment. Ethanol may perturb TGF-ß family receptors and signaling activities, including the sonic hedgehog pathway. Significantly, experiments show that activation of sonic hedgehog signaling rescues some embryonic ethanol exposure effects. More research is needed to understand how ethanol affects early developmental signaling and morphogenesis.