Retinoic acid X receptor in the diploblast, Tripedalia cystophora

Abstract

Nuclear hormone receptors comprise a characteristic family of transcription factors found in vertebrates, insects and nematodes. Here we show by cDNA and gene cloning that a Cnidarian, Tripedalia cystophora, possesses a retinoid receptor (jRXR) with remarkable homology to vertebrate retinoic acid X receptors (RXRs). Like vertebrate RXRs, jRXR binds 9-cis retinoic acid (K d ‫؍‬ 4 ؋ 10 ؊10 M) and binds to the DNA sequence, PuGGTCA as a monomer in vitro. jRXR also heterodimerizes with Xenopus TR beta on a thyroid responsive element of a direct repeat separated by 4 bp. A jRXR binding half-site capable of interacting with (His 6 )jRXR fusion protein was identified in the promoters of three T. cystophora crystallin genes that are expressed highly in the eye lens of this jellyfish. Because crystallin gene expression is regulated by retionoid signaling in vertebrates, the jellyfish crystallin genes are candidate in vivo targets for jRXR. Finally, an antibody prepared against (His 6 )jRXR showed that fulllength jRXR is expressed at all developmental stages of T. cystophora except the ephydra, where a smaller form replaces is. These data show that Cnidaria, a diploblastic phylum ancestral to the triploblastic invertebrate and subsequent vertebrate lineages, already have an RXR suggesting that RXR is an early component of the regulatory mechanisms of metazoa.

Retinoic acid signaling in development: Tissue‐specific functions and evolutionary origins

“…However, the absence of rxr in these two animals might be due to species-specific losses, because likely rxr homologs have been identified before in both cnidarians (Kostrouch et al, 1998) and nematodes (Shea et al, 2004). In general, this wide distribution of rxr genes in metazoan animals is consistent with a role of RXR proteins as heterodimeric binding partners of a whole suite of different nuclear receptors including RAR (reviewed in Gronemeyer et al, 2004).…”

Retinoid X receptors: X-ploring their (patho)physiological functions

“…It is interesting to note that the LBDs of the RXRs share a high degree of similarity from jellyfish to humans, all showing binding specificity for 9-cis RA as ligand. 44 An intriguing observation is that the early RXR homologue in jellyfish was capable of monomeric DNA binding. Jellyfish RXR binds 9-cis RA and probably induces transcription also.…”

“…Cnidarians (coelenterates), which include jelly fish and sea anemones, were reported as the earliest metazoans in which nuclear receptors emerged. 44 Interestingly, these organisms express Group 2 and 5 receptors: RXR, COUP-TF homologue and an FTF-F1 homologue. Very recently, a nuclear receptor was identified in a sponge, Suberites domuncula, which belongs to Group 2, indicating that nuclear receptors were present at the base of metazoan evolution and RXR homologues might be indeed the most ancient members of the family.…”

Phylogenetic evidence for the modular evolution of metazoan signalling pathways

“…Only few studies of NR function have been performed in non-bilaterian animals. Notably, signalling through the RXR receptor has been examined in several species of cnidarian; exogenous application of retinoic acid has been shown to play a role in promoting metamorphosis in the jellyfish Aurelia aurita [94] and regulating the development of the eyes in the box jelly Tripedalia cystophora [95]. Further, the COUP-TF transcription factor (NR2 family) is an important regulator of neurogenesis in hydrozoans [96,97].…”