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

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 functio...

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Bibliographic Details
Published in:Annual review of pharmacology and toxicology 2006-01, Vol.46 (1), p.451-480
Main Authors: MARK, Manuel, GHYSELINCK, Norbert B, CHAMBON, Pierre
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Embryology: invertebrates and vertebrates. Teratology
Embryonic Development - drug effects
Embryonic Development - genetics
Female
Fundamental and applied biological sciences. Psychology
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
Teratology. Teratogens
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Summary: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.
ISSN:0362-1642
1545-4304
DOI:10.1146/annurev.pharmtox.46.120604.141156