Ethanol downregulates gastrula gene expression and cell movement, causing symptoms of foetal alcohol spectrum disorders

Abstract

Foetal alcohol spectrum disorders (FASDs) occur in embryos when they are exposed to maternally supplied alcohol. To study the mechanisms of FASDs, the zebrafish embryo can serve as an excellent model as ethanol-exposed zebrafish embryos exhibit common symptoms of human FASDs including microcephaly, incomplete neural plate closure, eye defects, craniofacial disorders and many other defects. Here, we investigated the embryo development at gastrula stage where three germ layers develop with specific gene expressions and undergo dynamic cell movement including extension, convergence and epiboly, establishing the platform to form the head and body axis in later development. Gastrula cell movement analyses using fluorescent transgenic zebrafish embryos revealed that ethanol induced dose-dependent delay of extension, convergence and epiboly cell movement and associated gene expression in all three germ layers. Our results suggest multiple targets of ethanol including gene expression and cell movement, which, consequently, delay key gene expression and cell localisation, causing irreversible developmental defects in the head and body axis formation.