title: High-throughput RNA sequencing reveals the effects of 2,2',4,4' -tetrabromodiphenyl ether on retina and bone development of zebrafish larvae.
abstract: BACKGROUND
  2,2',4,4'-Tetrabromodiphenyl ether (BDE47) is a prevalent environmental pollutant and has been demonstrated to be a serious toxicant in both humans and animals, but little is known about the molecular mechanism underlying its toxic effect on the early development of vertebrates. BDE47-treated zebrafish larvae were found to present the light-related locomotion reduction in our previous study, therefore, we aimed to use high throughput sequencing to investigate the possible reasons from a transcriptomic perspective.
  
  
  RESULTS
  By exposing zebrafish embryos/larvae to 5 μg/l and 500 μg/l BDE47, we measured the influence of BDE47 on the mRNA expression profiles of zebrafish larvae until 6 days post-fertilization, using Illumina HiSeq 2000 sequencing. Differential expression analysis and gene enrichment analysis respectively revealed that a great number of genes, and gene sets based on two popular terminologies, were affected by the treatment of 500 μg/l BDE47. Among them, BDE47 caused changes in the retinal metabolism and related biological processes involving eye morphogenesis and visual perception, as confirmed by disordered photoreceptor arrangement and thickened bipolar cell layer of larval retina from histological observations. Other altered genes such as pth1a and collaborative cathepsin family exhibited disrupted bone development, which was consistent with the body curvature phenotype. The transcriptome of larvae was not significantly affected by the treatment of 5 μg/l BDE47, as well as the treatment of DMSO vehicle.
  
  
  CONCLUSIONS
  Our results suggest that high BDE47 concentrations disrupt the eye and bone development of zebrafish larvae based on both transcriptomic and morphological evidences. The abnormal visual perception may result in the alteration of dark adaption, which was probably responsible for the abnormal larval locomotion. Body curvature arose from enhanced bone resorption because of the intensive up-regulation of related genes. We also proposed the larval retina as a novel potential target tissue for BDE47 exposure.
authors.affiliation: Post-doctoral Research Station of Civil Engineering, Tongji University, Shanghai, 200092, China. 412_xuting@tongji.edu.cn.|Key Laboratory of Yangtze River Water Environment, Ministry of Education, College of Environmental Science and Technology, Tongji University, Shanghai, 200092, China. 412_xuting@tongji.edu.cn.
authors.forename: Ting
authors.initials: T
authors.lastname: Xu
authors.affiliation: Key Laboratory of Yangtze River Water Environment, Ministry of Education, College of Environmental Science and Technology, Tongji University, Shanghai, 200092, China. 412_zhaojing@tongji.edu.cn.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Yangtze River Water Environment, Ministry of Education, College of Environmental Science and Technology, Tongji University, Shanghai, 200092, China. yindq@tongji.edu.cn.
authors.forename: Daqiang
authors.initials: D
authors.lastname: Yin
authors.affiliation: Model Animal Research Center, MOE Key Laboratory of Model Animal for Disease Study, Nanjing University, Nanjing, 210061, China. qingshun@nju.edu.cn.
authors.forename: Qingshun
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: Post-doctoral Research Station of Civil Engineering, Tongji University, Shanghai, 200092, China. dbz77@tongji.edu.cn.
authors.forename: Bingzhi
authors.initials: B
authors.lastname: Dong
mesh_terms: D017398:Alternative Splicing / Q000187:drug effects; D000818:Animals; D001846:Bone Development / Q000187:drug effects*; D001842:Bone and Bones / Q000378:metabolism / Q000473:pathology; D005123:Eye / Q000473:pathology; D053263:Gene Regulatory Networks / Q000187:drug effects; D016678:Genome; D055768:Halogenated Diphenyl Ethers / Q000633:toxicity*; D059014:High-Throughput Nucleotide Sequencing; D007814:Larva / Q000235:genetics / Q000378:metabolism; D010786:Photoreceptor Cells / Q000378:metabolism; D012160:Retina / Q000187:drug effects* / Q000378:metabolism; D017423:Sequence Analysis, RNA; D059467:Transcriptome / Q000187:drug effects; D015027:Zebrafish / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism
chemical_list: D055768:Halogenated Diphenyl Ethers; C511295:2,2',4,4'-tetrabromodiphenyl ether