|ZFIN ID: ZDB-PUB-150822-7|
Transcriptional responses and mechanisms of copper-induced dysfunctional locomotor behavior in zebrafish embryos
Zhang, T., Xu, L., Wu, J.J., Wang, W.M., Mei, J., Ma, X.F., Liu, J.X.
|Source:||Toxicological sciences : an official journal of the Society of Toxicology 148(1): 299-310 (Journal)|
|Registered Authors:||Liu, Jing-xia, Zhang, Ting|
|Keywords:||copper, dysfunctional locomotor behavior, high-throughput in situ hybridization screening, myogenesis, neurogenesis|
|PubMed:||26293553 Full text @ Toxicol. Sci.|
Zhang, T., Xu, L., Wu, J.J., Wang, W.M., Mei, J., Ma, X.F., Liu, J.X. (2015) Transcriptional responses and mechanisms of copper-induced dysfunctional locomotor behavior in zebrafish embryos. Toxicological sciences : an official journal of the Society of Toxicology. 148(1):299-310.
ABSTRACTCopper-induced delayed hatching and dysfunctional movement had been reported previously, and unbalanced free copper was found in the body of humans with Alzheimer's disease and other neural diseases, but details of the underlying mechanisms are still unknown. In this study, zebrafish (Danio rerio) embryos exposed to over 3.9μM of copper exhibited delayed hatching and significantly dysfunctional movement. Using high-throughput in situ hybridization screening and by conducting an in-depth analysis of gene characterization in embryos exposed to copper, we found that copper caused neural crest defects from the initiation stage of neurogenesis, and embryos younger than the 70% epiboly stage were sensitive to copper toxicity. The myelination of Schwann cells, other than melanophores, cartilage, and neurons, was inhibited by copper during neurogenesis. In addition, axon guidance was blocked by copper. Down-regulated cdx4-hox might have contributed to the neurogenesis-related defects. Moreover, copper inhibited the differentiation of muscle fibers and myotomes but not the specification of muscle progenitors. In summary, our data reveal a novel molecular mechanism for copper-inhibited locomotor behavior in embryos, in which copper blocks functional muscle fiber specification during myogenesis and inhibits the specification of axons and Schwann cell myelination during neurogenesis. A combination of these processes results in dysfunctional locomotor behavior in zebrafish embryos exposed to copper.
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