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

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。鱼类的产卵栖息地遭受石油污染后极易受到损害，且原油可诱导胚胎与幼体出现严重发育异常。然而，此类发育缺陷的潜在分子机制尚未得到充分阐释。本研究针对具有商业价值的大西洋黑线鳕（Melanogrammus aeglefinus）早期生活史阶段，探究其受原油损伤后四种独立表型的转录调控基础。这四种表型分别为：(1) 心脏形态与功能缺陷；(2) 颅面发育异常；(3) 离子调节与体液平衡失衡；(4) 胆固醇合成与稳态紊乱。研究结果显示，细胞内钙循环与兴奋-转录偶联过程的失调，在心脏与颌骨形态发生异常中起到关键调控作用。此外，离子调节通路的紊乱为解析海水鱼类胚胎的浮力调控机制提供了全新视角。总体而言，本研究通过化学遗传学方法，明确了不同不良结局通路的起始事件，并揭示了单个基因在基础发育过程中的全新功能。