Campo-Paysaa Florent, Jandzik David, Takio-Ogawa Yoko, Cattell Maria V, Neef Haley C, Langeland James A, Kuratani Shigeru, Medeiros Daniel M, Mazan Sylvie, Kuraku Shigehiro, Laudet Vincent, Schubert Michael
Molecular Zoology Team, Institut de Génomique Fonctionnelle de Lyon, Université de Lyon, Université Lyon 1, CNRS, INRA, Ecole Normale Supérieure de Lyon, 69364 Lyon Cedex 07, France ; MRC Centre for Developmental Neurobiology, New Hunt's House, King's College London, Guy's Campus, London, SE1 1UL UK.
Department of Ecology and Evolutionary Biology, University of Colorado Boulder, Ramaley Biology, 1800 Colorado Avenue, Boulder, CO 80309 USA ; Department of Zoology, Comenius University in Bratislava, Mlynska Dolina B-1, 84215 Bratislava, Slovakia.
Evodevo. 2015 May 7;6:18. doi: 10.1186/s13227-015-0016-4. eCollection 2015.
Retinoic acid (RA) signaling controls many developmental processes in chordates, from early axis specification to late organogenesis. The functions of RA are chiefly mediated by a subfamily of nuclear hormone receptors, the retinoic acid receptors (RARs), that act as ligand-activated transcription factors. While RARs have been extensively studied in jawed vertebrates (that is, gnathostomes) and invertebrate chordates, very little is known about the repertoire and developmental roles of RARs in cyclostomes, which are extant jawless vertebrates. Here, we present the first extensive study of cyclostome RARs focusing on three different lamprey species: the European freshwater lamprey, Lampetra fluviatilis, the sea lamprey, Petromyzon marinus, and the Japanese lamprey, Lethenteron japonicum.
We identified four rar paralogs (rar1, rar2, rar3, and rar4) in each of the three lamprey species, and phylogenetic analyses indicate a complex evolutionary history of lamprey rar genes including the origin of rar1 and rar4 by lineage-specific duplication after the lamprey-hagfish split. We further assessed their expression patterns during embryonic development by in situ hybridization. The results show that lamprey rar genes are generally characterized by dynamic and highly specific expression domains in different embryonic tissues. In particular, lamprey rar genes exhibit combinatorial expression domains in the anterior central nervous system (CNS) and the pharyngeal region.
Our results indicate that the genome of lampreys encodes at least four rar genes and suggest that the lamprey rar complement arose from vertebrate-specific whole genome duplications followed by a lamprey-specific duplication event. Moreover, we describe a combinatorial code of lamprey rar expression in both anterior CNS and pharynx resulting from dynamic and highly specific expression patterns during embryonic development. This 'RAR code' might function in regionalization and patterning of these two tissues by differentially modulating the expression of downstream effector genes during development.
视黄酸（RA）信号传导控制着脊索动物从早期轴的特化到晚期器官发生的许多发育过程。RA的功能主要由核激素受体亚家族视黄酸受体（RARs）介导，RARs作为配体激活的转录因子发挥作用。虽然RARs在有颌脊椎动物（即gnathostomes）和无脊椎脊索动物中已得到广泛研究，但对于圆口纲动物（现存的无颌脊椎动物）中RARs的种类及其发育作用却知之甚少。在此，我们首次对圆口纲动物的RARs进行了广泛研究，重点关注三种不同的七鳃鳗物种：欧洲淡水七鳃鳗（Lampetra fluviatilis）、海七鳃鳗（Petromyzon marinus）和日本七鳃鳗（Lethenteron japonicum）。
我们在三种七鳃鳗物种中各鉴定出四个rar旁系同源基因（rar1、rar2、rar3和rar4），系统发育分析表明七鳃鳗rar基因具有复杂的进化历史，包括在七鳃鳗 - 盲鳗分化后通过谱系特异性复制产生rar1和rar4。我们通过原位杂交进一步评估了它们在胚胎发育过程中的表达模式。结果表明，七鳃鳗rar基因通常在不同胚胎组织中具有动态且高度特异性的表达域。特别是，七鳃鳗rar基因在前中枢神经系统（CNS）和咽部区域表现出组合表达域。
我们的结果表明七鳃鳗基因组编码至少四个rar基因，并表明七鳃鳗rar基因补充源自脊椎动物特有的全基因组复制，随后是七鳃鳗特有的复制事件。此外，我们描述了七鳃鳗rar在前中枢神经系统和咽部的组合表达密码，这是由胚胎发育过程中动态且高度特异性的表达模式产生的。这种“RAR密码”可能通过在发育过程中差异调节下游效应基因的表达，在这两种组织的区域化和模式形成中发挥作用。
