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 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.
Mark
Manuel
M
Institut de Génétique et de Biologie Moléculaire et Cellulaire, Institut Clinique de la Souris, Centre National de la Recherche Scientifique/INSERM, Université Louis Pasteur de Strasbourg, Collège de France, 67404 Illkirch Cedex, CU de Strasbourg, France.
Ghyselinck
Norbert B
NB
Chambon
Pierre
P
D000818:Animals; D047108:Embryonic Development / Q000187:drug effects* / Q000235:genetics*; D005260:Female; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D016296:Mutagenesis; D009153:Mutagens; D011247:Pregnancy; D018160:Receptors, Cytoplasmic and Nuclear / Q000187:drug effects / Q000235:genetics* / Q000502:physiology*; D018168:Receptors, Retinoic Acid / Q000187:drug effects / Q000235:genetics* / Q000502:physiology*; D047488:Retinoid X Receptors / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D012176:Retinoids / Q000633:toxicity; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics*; D013723:Teratogens
D009153:Mutagens; D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D012176:Retinoids; D013723:Teratogens