Ethanol Impairs Migration of the Prechordal Plate in the Zebrafish Embryo

Abstract

Exposure of vertebrate embryos to ethanol causes cyclopia, but little is known about the underlying mechanisms of this effect. Here we show that cyclopia can be induced in the zebrafish by a short ethanol treatment during early gastrula stages and is accompanied by loss of gene expression characteristic of the ventral aspects of the fore- and midbrain. Interestingly, defects in the expression of ventral brain markers are linked to impaired migration of the prechordal plate mesoderm indicating that the correct position of the prechordal plate mesoderm under the anterior neural plate in the zebrafish embryo is required for specification of the anterior neural midline. Ethanol-induced cyclopia does not, however, impair the induction of anterior neuroectodermal structures in general. Finally, as genes like goosecoid and islet-1 are expressed in prechordal plate cells in a temporal pattern similar to control embryos despite the ectopic position of expressing cells, it appears that regulation of prechordal plate-specific gene expression is largely independent of the final position of the prechordal plate.

Fetal alcohol exposure impairs hedgehog cholesterol modification and signaling

“…Exposure Recapitulate the Development Abnormities with Hh Signaling Defects As others have reported, 38 we found that alcohol-induced defects in zebrafish embryos recapitulated those that occurred in other species following fetal alcohol exposure. In a dose-dependent fashion, transient alcohol exposure for 6 h during gastrulation resulted in subsequent permanent phenotypic abnormalities while only a modest increase in the rate of embryo mortality was observed (Figure 1a).…”

“…41 Therefore, genetic or environmental factors that inhibit Shh signaling during gastrulation can disrupt proper patterning of the embryo. Interestingly, embryos that are exposed to alcohol during gastrulation 38 have defects that are similar to those found in embryos that have defects in Hh signal transduction. 42 A similar phenotype develops in embryos with a genetic defect in sterol homeostasis, for example, Smith-Lemli-Opitz Syndrome 43 or that are exposed to cholesterol lowering agents.…”

“…38 Embryos with chorions were exposed to six different concentrations of alcohol (eg, 0, 0.25, 0.5, 1.0, 1.5, and 2.0% (v/v)) in embryo medium. Embryos in sealed Petri dishes were exposed to alcohol for 6 h beginning at the dome stage (ie, 4.25 hours post-fertilization (hpf) or 30% epiboly stage) and were incubated at 28.51C.…”

“…Alcohol can also impair prechordal plate migration 38 and disrupt the formation and function of Spemann's Organizer, 39 a signaling center in gastrulating embryos that controls the patterning of the germ layers; the specific mechanisms that regulate axis pattern formation require highly evolutionarily conserved genetic pathways involving transcription regulatory circuitry and signal transduction pathways. 40 Shhcontaining vesicles contained within the organizer initiate a signal transduction pathway that plays a key role in embryonic patterning during development.…”

Japanese medaka (Oryzias latipes): developmental model for the study of alcohol teratology

“…In zebrafish, ethanol causes cyclopia, affects visual functions, induces pericardial edema and otolith defects, lowers heart rate, reduces eye diameter, induces axial malformations, delays development, and produces axial blistering (Bilotta et al, 2002(Bilotta et al, , 2004Reimers et al, 2004a). In addition, ethanol exposure has been shown to alter gene expression in the ventral aspects of the fore-and mid-brain (Blader and Strahle, 1998). Furthermore, in the zebrafish embryo, ethanol induces heat shock proteins Lele et al, 1997), produces developmental abnormalities of the notochord and spinal cord, and malformation of the body trunk (Baumann and Sander, 1984).…”