title: Transcriptional Responses and Mechanisms of Copper-Induced Dysfunctional Locomotor Behavior in Zebrafish Embryos.
abstract: Copper-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 3.9 μM 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. Downregulated 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.
authors: Key Laboratory of Freshwater Animal Breeding, Ministry of Agriculture, College of Fisheries, Huazhong Agricultural University, Wuhan 430070, China.
authors: Ting
authors: T
authors: Zhang
authors: Key Laboratory of Freshwater Animal Breeding, Ministry of Agriculture, College of Fisheries, Huazhong Agricultural University, Wuhan 430070, China.
authors: Lian
authors: L
authors: Xu
authors: Key Laboratory of Freshwater Animal Breeding, Ministry of Agriculture, College of Fisheries, Huazhong Agricultural University, Wuhan 430070, China.
authors: Jun-Jie
authors: JJ
authors: Wu
authors: Key Laboratory of Freshwater Animal Breeding, Ministry of Agriculture, College of Fisheries, Huazhong Agricultural University, Wuhan 430070, China.
authors: Wei-Min
authors: WM
authors: Wang
authors: Key Laboratory of Freshwater Animal Breeding, Ministry of Agriculture, College of Fisheries, Huazhong Agricultural University, Wuhan 430070, China.
authors: Jie
authors: J
authors: Mei
authors: Key Laboratory of Freshwater Animal Breeding, Ministry of Agriculture, College of Fisheries, Huazhong Agricultural University, Wuhan 430070, China xufama@mail.hzau.edu.cn ichliu@mail.hzau.edu.cn.
authors: Xu-Fa
authors: XF
authors: Ma
authors: Key Laboratory of Freshwater Animal Breeding, Ministry of Agriculture, College of Fisheries, Huazhong Agricultural University, Wuhan 430070, China xufama@mail.hzau.edu.cn ichliu@mail.hzau.edu.cn.
authors: Jing-Xia
authors: JX
authors: Liu
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects / Q000378:metabolism; D001522:Behavior, Animal / Q000187:drug effects*; D015415:Biomarkers / Q000378:metabolism; D003300:Copper / Q000633:toxicity*; D004625:Embryo, Nonmammalian / Q000002:abnormalities / Q000187:drug effects* / Q000378:metabolism; D047108:Embryonic Development / Q000187:drug effects; D029941:Fish Proteins / Q000235:genetics / Q000378:metabolism*; D017403:In Situ Hybridization; D009043:Motor Activity / Q000187:drug effects*; D024510:Muscle Development / Q000187:drug effects; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism; D009186:Myelin Sheath / Q000187:drug effects / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009432:Neural Crest / Q000002:abnormalities / Q000187:drug effects / Q000196:embryology; D055495:Neurogenesis / Q000187:drug effects; D012583:Schwann Cells / Q000187:drug effects / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects*; D014874:Water Pollutants, Chemical / Q000633:toxicity*; D015027:Zebrafish
chemical_list: D015415:Biomarkers; D029941:Fish Proteins; D009124:Muscle Proteins; D009419:Nerve Tissue Proteins; D014874:Water Pollutants, Chemical; D003300:Copper
keywords: copper; dysfunctional locomotor behavior; high-throughput in situ hybridization screening; myogenesis; neurogenesis