Abstract
BackgroundRetinoic 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.ResultsWe 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.ConclusionsOur 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s13227-015-0016-4) contains supplementary material, which is available to authorized users.
Highlights
Retinoic acid (RA) signaling controls many developmental processes in chordates, from early axis specification to late organogenesis
The newly characterized fourth rar gene was subsequently identified in the genomes of both P. marinus [32] and L. japonicum [37] and validated in P. marinus by polymerase chain reaction (PCR)-based cloning from complementary deoxyribonucleic acid (cDNA)
We further assessed the developmental expression of the rar genes in these three lamprey species
Summary
Retinoic acid (RA) signaling controls many developmental processes in chordates, from early axis specification to late organogenesis. The functions of RA are mediated by a subfamily of nuclear hormone receptors, the retinoic acid receptors (RARs), that act as ligand-activated transcription factors. In the course of vertebrate development, for example, RA controls cell proliferation, cell differentiation, apoptosis, and cell survival, acting at different developmental stages, from early gastrulation to late organogenesis, and in all embryonic tissue layers. The molecular response to RA is controlled by heterodimers of two members of the nuclear hormone receptor superfamily: the retinoic acid receptor (RAR) and the retinoid X receptor (RXR) [6,7,8,9]. RAR/RXR target gene specificity is mediated by the binding of the heterodimer to specific DNA elements in the regulatory regions of target genes, the socalled retinoic acid response elements (RAREs) [10,11,12,13]
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