The Estrogen Related Receptor (ERR) nuclear hormone receptor genes have a wide diversity of roles in vertebrate development. In embryos, ERR genes are expressed in several tissues, including the central and peripheral nervous systems. Here we seek to establish the evolutionary history of chordate ERR genes, their expression and their regulation. We examine ERR expression in mollusc, amphioxus and sea squirt embryos, finding the single ERR orthologue is expressed in the nervous system in all three, with muscle expression also found in the two chordates. We show that most jawed vertebrates and lampreys have four ERR paralogues, and that vertebrate ERR genes were ancestrally linked to Estrogen Receptor genes. One of the lamprey paralogues shares conserved expression domains with jawed vertebrate ERRγ in the embryonic vestibuloacoustic ganglion, eye, brain and spinal cord. Hypothesising that conserved expression derives from conserved regulation, we identify a suite of pan-vertebrate conserved non-coding sequences in ERR introns. We use transgenesis in lamprey and chicken embryos to show that these sequences are regulatory and drive reporter gene expression in the nervous system. Our data suggest an ancient association between ERR and the nervous system, including expression in cells associated with photosensation and mechanosensation. This includes the origin in the vertebrate common ancestor of a suite of regulatory elements in the 3’ introns that drove nervous system expression and have been conserved from this point onwards.

雌激素相关受体( ERR ) 核激素受体基因在脊椎动物发育中发挥着广泛的作用。在胚胎中，ERR 基因在多种组织中表达，包括中枢和周围神经系统。在这里，我们试图建立脊索动物ERR基因的进化史、它们的表达和调控。我们检查了软体动物、文昌鱼和海鞘胚胎中的ERR表达，发现单个ERR直系同源物在这三种动物的神经系统中表达，并且在两种脊索动物中也发现了肌肉表达。我们发现大多数有颌脊椎动物和七鳃鳗有四个ERR旁系同源物，并且脊椎动物的ERR基因与雌激素受体基因有祖先联系。其中一种七鳃鳗旁系同源物与有颌脊椎动物胚胎前庭声学神经节、眼睛、大脑和脊髓中的ERRγ具有保守的表达域。假设保守表达源自保守调控，我们在ERR内含子中鉴定了一套泛脊椎动物保守非编码序列。我们在七鳃鳗和鸡胚胎中使用转基因来证明这些序列具有调节性并驱动神经系统中的报告基因表达。我们的数据表明ERR与神经系统之间存在古老的关联，包括与光感和机械感相关的细胞中的表达。这包括 3' 内含子中一系列调控元件起源于脊椎动物共同祖先，这些元件驱动神经系统表达，并从此时起一直保留下来。