Neurodevelopmental Defects in Zebrafish (Danio rerio) at Environmentally Relevant Dioxin (TCDD) Concentrations

Abstract

Persistent ecotoxicants, such as dioxin and PCBs, are thought to pose one of the greatest threats to public and ecological health in the industrial world. These compounds cause a range of macroscopic malformations, particularly to the craniofacial apparatus and cardiovascular system during vertebrate development. However, little is known about microscopic effects, especially on the sensitive early life stages or on the molecular basis of developmental neurotoxicity. Using zebrafish (Danio rerio), we have explored neurological deficits caused by early-life exposure to environmentally relevant concentrations of dioxin. We show, using a quantitative stereological technique, that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) substantially reduces the capacity for embryonic brain development, causing a 30% reduction in total neuronal number in the 168-h larval brain. Using transgenic GFP-expressing zebrafish lines, we link this to decreased expression of key developmentally regulated genes, namely neurogenin and sonic hedgehog. This disruption of neuronal development provides the basis for understanding the neurotoxic effects of these compounds.

Potential Roles of Arnt2 in Zebrafish Larval Development

“…Whole-mount ISH was used to determine if the pattern or intensity of staining for sim1 (zebrafish single-minded homolog 66 ), as well as for krox20, pax6a, and islet1, 67 were altered in the brain of arnt2 À=À mutant zebrafish. ISH was performed as described by Oxtoby and Jowett 68 using digoxigenin (DIG)-labeled probes (labeled in accordance with the Roche DIG RNA labeling protocol) and detected using anti-DIG alkaline phosphatase (AP; 1:4000, v:v) and BCIP=NBT substrate.…”

Amin A. Milki and Sunny H. Jun 9. Transcriptome Analysis of Mouse Stem Cells and Early Embryos

“…Functional studies of TCDD toxicity in the zebrafish embryo well illustrate this (reviewed in [39]). Forward genetics [40][41][42][43], targeting-induced local lesions in genomes (TILLING) [40], morpholino knockdown [44], transgenesis [38,45] and in situ expression studies [46,47] at cellular resolution represent a powerful technical repertoire for dissecting toxicological pathways. Moreover, a large number of developmental mutants have been isolated, some of which may serve as direct targets for drugs and toxicants [48,49].…”

Making a difference together: reciprocal interactions in C. elegans and zebrafish asymmetric neural development

“…Although there is a considerable evolutionary gulf between the 302 neurons of the nematode and the estimated 78,000 neurons of the larval zebrafish (Hill et al, 2003), some common themes arise, in particular the interaction of neurons across the midline during the formation of the lateralized nervous system and the inherently stochastic nature of some developmental pathways. However, the striking differences in the genetic and cellular pathways highlight the improbability that nematode and zebrafish brain asymmetry arose from a shared ancestral event.…”

“…We first discuss the specification of the left and right amphid wing 'C' (AWC) neurons of the C. elegans olfactory system, which is influenced by calcium influx; this, in turn, is regulated by gap junction-and claudin-mediated cell-cell communication. We then discuss the development of asymmetry in the zebrafish epithalamus, where Nodal signaling initiates a series of reciprocal interactions between the left-sided parapineal organ and the left habenular nucleus.Although there is a considerable evolutionary gulf between the 302 neurons of the nematode and the estimated 78,000 neurons of the larval zebrafish (Hill et al, 2003), some common themes arise, in particular the interaction of neurons across the midline during the formation of the lateralized nervous system and the inherently stochastic nature of some developmental pathways. However, the striking differences in the genetic and cellular pathways highlight the improbability that nematode and zebrafish brain asymmetry arose from a shared ancestral event.…”