在过去的20年里,斑马鱼(Daniorerio)已成为揭示由芳烃受体(AHR)介导的分子信号事件的恒星模型,在所有Eumetazoan动物中发现的一种重要的配体激活受体。斑马鱼有3个AHRs-AHR1a,AHR1b,和AHR2,研究表明斑马鱼AHR的内源性和毒理学功能的多样性。在这篇当代评论中,我们首先强调斑马鱼ahr基因的进化,以及受体的特征,包括发育和成人表达,它们的内源和诱导作用,以及来自同源建模研究的预测配体。然后,我们回顾了跨多个生命阶段的广谱AHR配体的毒性(早期,和成人),讨论它们的转录组和表观遗传作用机制,并报告AHR与其他信号通路之间的任何已知相互作用。通过这篇文章,我们总结了有希望的研究,通过广泛使用斑马鱼作为模型,进一步加深了我们对复杂AHR途径的理解,加上大量的分子技术。由于许多研究都集中在AHR2在开发过程中的功能以及TCDD(2,3,7,8-四氯二苯并对二恶英)毒性的机制上,我们说明了在理解AHR1a和AHR1b的机制作用时,需要解决相当大的知识差距,以及各种AHR配体的多种毒性模式。
Over the last 2 decades, the zebrafish (Danio rerio) has emerged as a stellar model for unraveling molecular signaling events mediated by the aryl hydrocarbon receptor (AHR), an important ligand-activated receptor found in all eumetazoan animals. Zebrafish have 3 AHRs-AHR1a, AHR1b, and AHR2, and studies have demonstrated the diversity of both the endogenous and toxicological functions of the zebrafish AHRs. In this contemporary
review, we first highlight the evolution of the zebrafish ahr genes, and the characteristics of the receptors including developmental and adult expression, their endogenous and inducible roles, and the predicted ligands from homology modeling studies. We then
review the toxicity of a broad spectrum of AHR ligands across multiple life stages (early stage, and adult), discuss their transcriptomic and epigenetic mechanisms of action, and report on any known interactions between the AHRs and other signaling pathways. Through this article, we summarize the promising research that furthers our understanding of the complex AHR pathway through the extensive use of zebrafish as a model, coupled with a large array of molecular techniques. As much of the research has focused on the functions of AHR2 during development and the mechanism of TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) toxicity, we illustrate the need to address the considerable knowledge gap in our understanding of both the mechanistic roles of AHR1a and AHR1b, and the diverse modes of toxicity of the various AHR ligands.