Outside the chordate lineage, however, evidence for functional roles of retinoids and of the RAR/RXR heterodimer remains scarce. Although we have been able to identify genes encoding orthologs of vertebrate RALDH and CYP26 as well as of vertebrate RAR and RXR in ambulacrarian deuterostomes (such as hemichordates and echinoderms) and lophotrochozoan protostomes (such as annelids and mollusks), extensive experimental evidence for retinoid and/or RAR/RXR functions in these animal lineages is still lacking. Previous analyses based on pharmacological treatments have nonetheless suggested that retinoids may have distinct effects during echinoderm, annelid, and mollusk embryogenesis. Moreover, retinoids have also been implicated in tissue regeneration of insects and crustaceans and in cell proliferation and neuronal differentiation of cnidarians, all of which are animals, whose genomes do not encode a RAR. Collectively, these data hence suggest that functions for retinoids as morphogens originated before a functional RAR/RXR heterodimer and, given the importance of the RAR/RXR heterodimer for mediating retinoid signaling in chordates, evoke the question of the evolutionary origins of the ligand binding capacities of RAR and RXR.

Using a combination of molecular, developmental, and genomic approaches, in the EvoInSiDe team, we are thus currently characterizing the functions of retinoids and of RAR and RXR in various animal lineages, including lophotrochozoans, ambulacrarians, invertebrate chordates, and vertebrates. Comparisons of these respective functions will reveal roles for retinoids that are dependent on RAR and RXR and those that are independent of the receptors. Moreover, cross-comparisons of these results between the different species will identify conserved and divergent elements of retinoid signaling, which in turn will allow the reconstruction of the evolutionary diversification of this morphogen-dependent signaling cascade in bilaterian animals.