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Retinoid-X receptor action and disruption in development
Brenda J Mengeling1, J David Furlow1
1Department of Neurobiology, Physiology, and Behavior, College of Biological Sciences, University of California Davis, Davis, CA, USA.
Abstract:
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.
Insights
Retinoid X receptor (RXR) is crucial for animal development, acting as a key partner for other nuclear receptors. This review explores RXR's ancient roles, its ligands, and how environmental chemicals can disrupt its signaling during development.
Area of Science:
- Developmental Biology
- Molecular Endocrinology
- Evolutionary Biology
Background:
- Retinoid X receptor (RXR) is a vital nuclear receptor (NR) superfamily member.
- RXR acts as an essential heterodimer partner for numerous other NRs, including RARs, TRs, VDR, and PPARs.
- RXR is ancient, with roles in development across diverse metazoan lineages.
Purpose of the Study:
- To review the diverse roles of RXRs in animal development, particularly in metamorphic genetic programs.
- To explore the ongoing research into RXR's endogenous ligands and their requirement for RXR action.
- To discuss mechanisms controlling RXR availability for NR partnership and the impact of environmental chemicals on RXR signaling.
Main Methods:
- Literature review of existing studies on RXR function in animal development.
- Analysis of evolutionary conservation of RXR across metazoan phyla.
- Synthesis of current cellular data and environmental toxicology findings related to RXR.
Main Results:
- RXR plays critical roles in developmental programs across the animal kingdom.
- Understanding of RXR's endogenous ligands and their precise roles remains an active area of research.
- Environmental chemicals can interfere with RXR signaling, potentially disrupting development.
Conclusions:
- RXR is a fundamental regulator of animal development with ancient evolutionary origins.
- Further research is needed to fully elucidate RXR ligand interactions and regulatory mechanisms.
- Protecting against environmental disruptors of RXR signaling is important for healthy development.
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