Evolutionary Conservation in Retinoid Signalling and Metabolism

In accord with the notion that retinoid signalling is of central importance in vertebrate evolution, a number of its components are evolutionarily conserved. Retinoid X nuclear receptors (RXRs), which interact directly with a number of signalling pathways, are highly conserved among mammals, Xenopus, and chick. We have studied RXRs in zebrafish and find that they are also very well conserved with respect to amino acid sequence and function, compared to mammalian RXRs. However, zebrafish has additional subtypes (RXRδ and RXRε) which are altered in structure and function. New information which has come to light since these were first described suggests ways in which these unique subtypes could fine-tune retinoid signalling in zebrafish. We have performed phylogenetic analysis with the zebrafish RXRs and RXRs from other species to try to understand the evolutionary relationships among them. In addition, we have found a retinoic acid (RA)-inducible, RA-metabolizing cytochrome P450 (P450RAI/CYP26) which is evolutionarily conserved among vertebrates and has an important role in controlling retinoid signalling by regulating the level of biologically available RA.