Vuori Kristiina A, Nordlund Eija, Kallio Jenny, Salakoski Tapio, Nikinmaa Mikko
Centre of Excellence in Evolutionary Genetics and Physiology, Department of Biology, University of Turku, FI-20014 Turku, Finland.
Aquat Toxicol. 2008 Apr 8;87(1):19-27. doi: 10.1016/j.aquatox.2008.01.006. Epub 2008 Jan 18.
The aryl hydrocarbon receptor (AhR) is an ancient protein that is conserved in vertebrates and invertebrates, indicating its important function throughout evolution. AhR has been studied largely because of its role in toxicology-gene expression via AhR is induced by many aromatic hydrocarbons in mammals. Recently, however, it has become clear that AhR is involved in various aspects of development such as cell proliferation and differentiation, and cell motility and migration. The mechanisms by which AhR regulates these various functions remain poorly understood. Across-species comparative studies of AhR in invertebrates, non-mammalian vertebrates and mammals may help to reveal the multiple functions of AhR. Here, we have studied AhR during larval development of Baltic salmon (Salmon salar). Our results indicate that AhR protein is expressed in nervous system, liver and muscle tissues. We also present putative regulatory modules and module-matching genes, produced by chromatin immunoprecipitation (ChIP) cloning and in silico analysis, which may be associated with evolutionarily conserved functions of AhR during development. For example, the module NFKB-AHRR-CREB found from salmon ChIP sequences is present in human ULK3 (regulating formation of granule cell axons in mouse and axon outgrowth in Caernohabditis elegans) and SRGAP1 (GTPase-activating protein involved in the Slit/Robo pathway) promoters. We suggest that AhR may have an evolutionarily conserved role in neuronal development and nerve cell targeting, and in Wnt signaling pathway.
芳基烃受体（AhR）是一种古老的蛋白质，在脊椎动物和无脊椎动物中都保守存在，这表明它在整个进化过程中具有重要功能。对AhR的研究主要是因为它在毒理学中的作用——在哺乳动物中，许多芳香烃可诱导AhR介导的基因表达。然而，最近人们清楚地认识到，AhR参与了发育的各个方面，如细胞增殖与分化、细胞运动和迁移。AhR调节这些不同功能的机制仍知之甚少。对无脊椎动物、非哺乳动物脊椎动物和哺乳动物中的AhR进行跨物种比较研究，可能有助于揭示AhR的多种功能。在此，我们研究了波罗的海鲑鱼（Salmo salar）幼体发育过程中的AhR。我们的结果表明，AhR蛋白在神经系统、肝脏和肌肉组织中表达。我们还展示了通过染色质免疫沉淀（ChIP）克隆和计算机分析产生的假定调控模块和模块匹配基因，它们可能与发育过程中AhR的进化保守功能相关。例如，从鲑鱼ChIP序列中发现的NFKB - AHRR - CREB模块存在于人类ULK3（调节小鼠颗粒细胞轴突形成和秀丽隐杆线虫轴突生长）和SRGAP1（参与Slit/Robo信号通路的GTP酶激活蛋白）的启动子中。我们认为，AhR可能在神经元发育、神经细胞靶向以及Wnt信号通路中具有进化保守作用。
