

As such, we developed a CNS Drosophila organ culture-based system to examine the transcriptional activity and ligand-binding properties of LymRXR, in the context of a live invertebrate nervous system. RXRs are predominantly nuclear receptors, but the Lymnaea RXR (LymRXR) exhibits a non-nuclear distribution in the adult CNS, where it is also implicated in non-genomic retinoid functions. We have shown that many of the effects of retinoids are conserved in the CNS of the mollusc, Lymnaea stagnalis.


Retinoic acid, the active metabolite of Vitamin A, is important for the appropriate development of the nervous system (e.g., neurite outgrowth) as well as for cognition (e.g., memory formation) in the adult brain. In this context, marine invertebrates have been crucial for characterizing the ancestral states of NR-ligand interactions, further strengthening the importance of these organisms in the field of evolutionary developmental biology. The explosion of genome sequencing projects and the interpretation of the resulting data in a phylogenetic context allowed significant progress toward an understanding of NR superfamily evolution, both in terms of molecular activities and developmental functions. Accumulating evidence suggests that NR signaling is also a major regulator of development in marine invertebrates, although ligands and transactivation dynamics are not necessarily conserved with respect to vertebrates. In vertebrates, NRs are pivotal players in countless processes of both embryonic and adult physiology, with embryonic development being one of the most dynamic periods of NR activity. Nuclear Receptors (NRs) are a superfamily of transcription factors specific to metazoans that have the unique ability to directly translate the message of a signaling molecule into a transcriptional response.
PLASTIC BERTRAND AN 1 RAR RAR
Our findings provide a timeline for RA signalling evolution in the Bilateria and give support to the hypothesis that the increase in RA affinity towards RAR is a late acquisition in the evolution of the Metazoa. We further demonstrate that the Priapulida RAR displays low-affinity for retinoids (similar to annelids), and is not responsive to common endocrine disruptors acting via RAR. By exploring a draft genome assembly, we show, by means of phylogenetics and functional assays, that an orthologue of the nuclear receptor retinoic acid receptor (RAR) subfamily, a central mediator of RA signalling, is present in Ecdysozoa, contrary to previous perception. Priapulids, with their slow rate of molecular evolution and phylogenetic position, represent a key taxon to investigate the early phases of Ecdysozoa evolution.

RA signalling has been shown to be central to chordate endocrine homeostasis, participating in multiple developmental and physiological processes. Here, we address the evolution of retinoic acid (RA) signalling in the Priapulida worm, Priapulus caudatus Lamarck, 1816, an Ecdysozoa. Defining their presence or absence in extant animal lineages is critical to accurately devise evolutionary patterns, physiological shifts and the impact of endocrine-disrupting chemicals. Signalling molecules and their cognate receptors are central components of the Metazoa endocrine system.
