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Developmental toxicology

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Expression and function of defensome genes and proteins in zebrafish

Zebrafish are being used as a model in all areas of environmental toxicology, for example to discern mechanisms, as a tool in testing, in monitoring the toxic potential in particular environments, in qualitative or quantitative screening of effluents for the presence of effective levels of toxicants, or in screening compounds for particular activities in hazard identification. There is enormous potential for that use to grow. We emphasize the mechanistic aspects, including new information on the genes that comprise the “defensome”. Toxicogenomic studies are uncovering the involvement of new genes, and pointing to the possibility of common mechanisms and pathways that are shared at least partly in different toxicological processes, such as wnt signaling involved in craniofacial defects in embryos and altered fin regeneration in adults. Other pathways are less well known. Placing defensome genes in gene regulatory networks is an open area, rich with possibilities. The metabolism and disposition of chemicals is strongly related to their toxicity. While we are learning much about the expression of genes that are implicated in these processes, study of the proteins themselves has lagged substantially. Strong inferences regarding effects of particular chemicals from results in this model organism require knowledge of the function of these proteins, whether enzymes, receptors or other transcription factors. Studies of many of the relevant genes and proteins in zebrafish are still emerging from the descriptive phase relative to the studies in mammals, but new tools and approaches in zebrafish are enabling a growing number of mechanistic advances. Examining similarities and differences between zebrafish and other species will lead to new fundamental understanding of the defense against and susceptibility to chemicals.

We use microarrays, qPCR, immunohistochemistry, and heterologous expression of CYPs, AKRs, and other genes.



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Expression and function of defensome genes and proteins in sea anemones

The starlet sea anemone Nematostella vectensis has been recently established as a new model system for the study of the evolution of developmental processes, as cnidaria occupy a key evolutionary position at the base of the bilateria. Cnidaria play important roles in estuarine and reef communities, but are exposed to many environmental stressors.

We described the genetic components of a ‘chemical defensome’ in the genome of N. vectensis, and with Ann Tarrant and Adam Reitzel have studied some of these genes. Gene families that defend against chemical stressors and the transcription factors that regulate these genes have been termed a ‘chemical defensome,’ and include the cytochromes P450 and other oxidases, various conjugating enzymes, the ATP-dependent efflux transporters, oxidative detoxification proteins, as well as various transcription factors. These genes account for about 1% (266/27200) of the predicted genes in the sea anemone genome, similar to the proportion observed in tunicates and humans, but lower than that observed in sea urchins. While there are comparable numbers of stress-response genes, the stress sensor genes appear to be reduced in N. vectensis relative to many model protostomes and deuterostomes. Cnidarian toxicology is understudied, especially given the important ecological roles of many cnidarian species. New genomic resources should stimulate the study of chemical stress sensing and response mechanisms in cnidaria, and allow us to further illuminate the evolution of chemical defense gene networks.




Last updated: September 5, 2012
 


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