CYP26 function is required for the tissue-specific modulation of retinoic acid signaling during amphioxus development

During development, morphogens, such as retinoic acid (RA), act as mediators of intercellular communication systems to control patterning and cell fate specification processes. In vertebrates, the tightly regulated production and degradation of RA creates an anterior-posterior (A-P) morphogen gradient that is required for regional patterning of the embryo. RA catabolism in particular, mediated by members of the cytochrome P450 subfamily 26 (CYP26), has been highlighted as a key regulatory component for the formation of this gradient. RA-dependent developmental patterning is now widely recognized as a shared feature of all chordate groups (i.e. of vertebrates, tunicates, and cephalochordates). However, the evolutionary origin of the RA morphogen gradient still remains elusive. Thus, in the present study, we used pharmacological approaches to assess the roles of CYP26 enzymes in tissue-specific patterning processes in embryos and larvae of the cephalochordate amphioxus (Branchiostoma lanceolatum). Marker gene analyses revealed selective requirements for CYP26 activity in anterior endoderm, general ectoderm as well as central nervous system (CNS), but not in mesoderm. Furthermore, comparisons of the effects induced by CYP26 inhibition with those obtained by the pharmacological upregulation or downregulation of global RA signaling levels yielded evidence for a role of CYP26 in establishing an A-P RA gradient in the amphioxus embryo, important at least for patterning the CNS. Altogether, this work hence highlights the involvement of CYP26 in tissue-specific modulations of RA signaling activity in the amphioxus embryo and suggests that a RA morphogen gradient already functioned in the last common ancestor of all chordates.