Abstract
Signalling molecules and their cognate receptors are central components of the Metazoa endocrine system. 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. Here, we address the evolution of retinoic acid (RA) signalling in the Priapulida worm, Priapulus caudatus Lamarck, 1816, an Ecdysozoa. RA signalling has been shown to be central to chordate endocrine homeostasis, participating in multiple developmental and physiological processes. Priapulids, with their slow rate of molecular evolution and phylogenetic position, represent a key taxon to investigate the early phases of Ecdysozoa evolution. 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. 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. 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.
Highlights
Retinoic acid (RA) is a critical regulator of multiple biological processes in vertebrates including cell differentiation and embryonic development [1,2], central nervous system development [3,4,5], organ formation and tissue maintenance [6,7,8] and vision [9]
The emergence of various non-chordate genome sequences established that retinoic acid (RA) signalling is not chordate-specific, since signalling components such as retinoic acid receptor (RAR) and retinoid X receptor (RXR) gene orthologues have been found in species from Ambulacraria [15,16,17,18,19,20]
By thoroughly examining a genome draft of P. caudatus, we established the presence of sequences with high similarity to RAR and RXR respectively
Summary
Retinoic acid (RA) is a critical regulator of multiple biological processes in vertebrates including cell differentiation and embryonic development [1,2], central nervous system development [3,4,5], organ formation and tissue maintenance [6,7,8] and vision [9]. Retinoids, such all-trans retinoic acid (ATRA), 9-cis retinoic acid (9cisRA) and 13-cis retinoic acid (13cisRA) are active metabolites of vitamin. In a second annelid species, Helobdella robusta (leech), RAR and other
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