Function of retinoid nuclear receptors: lessons from genetic and pharmacological dissections of the retinoic acid signaling pathway during mouse embryogenesis

Annu Rev Pharmacol Toxicol. 2006;46:451-80. doi: 10.1146/annurev.pharmtox.46.120604.141156.

Abstract

Retinoic acid (RA) is involved in vertebrate morphogenesis, growth, cellular differentiation, and tissue homeostasis. The use of in vitro systems initially led to the identification of nuclear receptor RXR/RAR heterodimers as possible transducers of the RA signal. To unveil the physiological functions of RARs and RXRs, genetic and pharmacological studies have been performed in the mouse. Together, their results demonstrate that (a) RXR/RAR heterodimers in which RXR is either transcriptionally active or silent are involved in the transduction of the RA signal during prenatal development, (b) specific RXRalpha/RAR heterodimers are required at many distinct stages during early embryogenesis and organogenesis, (c) the physiological role of RA and its receptors cannot be extrapolated from teratogenesis studies using retinoids in excess. Additional cell type-restricted and temporally controlled somatic mutagenesis is required to determine the functions of RARs and RXRs during postnatal life.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Embryonic Development / drug effects*
  • Embryonic Development / genetics*
  • Female
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Mutagenesis
  • Mutagens
  • Pregnancy
  • Receptors, Cytoplasmic and Nuclear / drug effects
  • Receptors, Cytoplasmic and Nuclear / genetics*
  • Receptors, Cytoplasmic and Nuclear / physiology*
  • Receptors, Retinoic Acid / drug effects
  • Receptors, Retinoic Acid / genetics*
  • Receptors, Retinoic Acid / physiology*
  • Retinoid X Receptors / drug effects
  • Retinoid X Receptors / genetics
  • Retinoid X Receptors / physiology
  • Retinoids / toxicity
  • Signal Transduction / drug effects*
  • Signal Transduction / genetics*
  • Teratogens

Substances

  • Mutagens
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Retinoic Acid
  • Retinoid X Receptors
  • Retinoids
  • Teratogens