Retinoid-X receptor action and disruption in development

Across the animal kingdom, many developmental programs require retinoid X receptor (RXR) expression. RXR is a unique member of the nuclear receptor (NRs) superfamily of transcription factors. Most famously, it serves as a mandatory heterodimer partner for a third of the other vertebrate NRs, such as retinoic acid receptors (RARs), thyroid hormone receptors (TRs), the vitamin D receptor (VDR), and peroxisome proliferator-activated receptors (PPARs), which all have important roles in development. RXR is also one of the most ancient NRs, with expression in most metazoan lineages going back to basal metazoans such as placozoans and cnidarians, and we review examples across the major animal phyla of RXRs diverse roles in animal development, especially in control of metamorphic genetic programs. We also review the open area of RXR research that seeks to determine the endogenous ligands of RXR and when and where they are required for RXR action. Further, we discuss the current understanding from cellular data with implications for development of how organisms may control the availability of RXR for NR partnership and the hierarchy of NR access to a limited RXR pool. Finally, we will review the ability of certain man-made chemicals in the environment to disrupt RXR signaling during development.