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Data from: Novel adverse outcome pathways revealed by chemical genetics in a developing marine fish

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DataONE2017-02-28 更新2024-06-26 收录
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Crude oil spills are a worldwide ocean conservation threat. Fish are particularly vulnerable to the oiling of spawning habitats, and crude oil causes severe abnormalities in embryos and larvae. However, the underlying mechanisms for these developmental defects are not well understood. Here, we explore the transcriptional basis for four discrete crude oil injury phenotypes in the early life stages of the commercially important Atlantic haddock (Melanogrammus aeglefinus). These include defects in (1) cardiac form and function, (2) craniofacial development, (3) ionoregulation and fluid balance, and (4) cholesterol synthesis and homeostasis. Our findings suggest a key role for intracellular calcium cycling and excitation-transcription coupling in the dysregulation of heart and jaw morphogenesis. Moreover, the disruption of ionoregulatory pathways sheds new light on buoyancy control in marine fish embryos. Overall, our chemical-genetic approach identifies initiating events for distinct adverse outcome pathways and novel roles for individual genes in fundamental developmental processes.

原油泄漏是全球性的海洋保护威胁。鱼类对产卵栖息地的油污染尤为敏感,且原油会引发胚胎与幼体出现严重畸形。然而,此类发育缺陷的潜在机制尚未得到充分阐明。本研究探讨了具有商业价值的大西洋黑线鳕(Melanogrammus aeglefinus)早期生命阶段中,四种独立的原油损伤表型的转录基础(transcriptional basis)。这四种表型分别为:(1) 心脏形态与功能异常;(2) 颅面发育缺陷;(3) 离子调节(ionoregulation)与体液平衡失衡;(4) 胆固醇合成及稳态紊乱。研究结果表明,细胞内钙循环与兴奋-转录偶联(excitation-transcription coupling)在心脏及颌部形态发生失调中发挥关键作用。此外,离子调节通路的紊乱为理解海水鱼类胚胎的浮力调控机制提供了新视角。总体而言,本研究采用的化学遗传学方法(chemical-genetic approach),为不同不良结局路径(adverse outcome pathways)确定了起始事件,并揭示了单个基因在基础发育过程中的全新功能。

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2017-02-28
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