Nuclear receptors comprise a superfamily of sequence-specific transcription factors whose members have diverse roles during development. This review will summarize the developmental roles of selected members of the nuclear receptor superfamily.
References
1.
Abu-AbedS., DolleP., MetzgerD., BeckettB., ChambonP., and PetkovichM. (2001). The retinoic acid-metabolizing enzyme, CYP26A1, is essential for normal hindbrain patterning, vertebral identity, and development of posterior structuresGenes Dev15, 226–40.
2.
AngH. L., and DuesterG. (1997). Initiation of retinoid signaling in primitive streak mouse embryos: spatiotemporal expression patterns of receptors and metabolic enzymes for ligand synthesisDev Dyn208, 536–43.
3.
BarakY., LiaoD., HeW., OngE. S., NelsonM. C., OlefskyJ. M., BolandR., and EvansR. M. (2002). Effects of peroxisome proliferator-activated receptor Δ on placentation, adiposity, and colorectal cancerProc Natl Acad Sci U S A99, 303–8.
4.
BarakY., NelsonM. C., OngE. S., JonesY. Z., Ruiz-LozanoP., ChienK. R., KoderA., and EvansR. M. (1999). PPAR γ is required for placental, cardiac, and adipose tissue developmentMol Cell4, 585–95.
5.
BarretoG., ReintschW., KaufmannC., and DreyerC. (2003a). The function of Xenopus germ cell nuclear factor (xGCNF) in morphogenetic movements during neurulationDev Biol257, 329–42.
6.
BarretoG., BorgmeyerU., and DreyerC. (2003b). The germ cell nuclear factor is required for retinoic acid signaling during Xenopus developmentMech Dev120, 415–28.
7.
BegemannG., and MeyerA. (2001). Hindbrain patterning revisited: timing and effects of retinoic acid signallingBioessays23, 981–6.
8.
ChenW. S., ManovaK., WeinsteinD. C., DuncanS. A., PlumpA. S., PreziosoV. R., BachvarovaR. F., and DarnellJ. E.Jr. (1994). Disruption of the HNF-4 gene, expressed in visceral endoderm, leads to cell death in embryonic ectoderm and impaired gastrulation of mouse embryosGenes Dev8, 2466–77.
9.
ChungA. C., KatzD., PereiraF. A., JacksonK. J., DeMayoF. J., CooneyA. J., and O'MalleyB. W. (2001). Loss of orphan receptor germ cell nuclear factor function results in ectopic development of the tail bud and a novel posterior truncationMol Cell Biol21, 663–77.
10.
DavidR., JoosT. O., and DreyerC. (1998). Anteroposterior patterning and organogenesis of Xenopus laevis require a correct dose of germ cell nuclear factor (xGCNF)Mech Dev79, 137–52.
11.
DolleP., RuberteE., LeroyP., Morriss-KayG., and ChambonP. (1990). Retinoic acid receptors and cellular retinoid binding proteins. I. A systematic study of their differential pattern of transcription during mouse organogenesisDevelopment110, 1133–51.
12.
DrewesT., SenkelS., HolewaB., and RyffelG. U. (1996). Human hepatocyte nuclear factor 4 isoforms are encoded by distinct and differentially expressed genesMol Cell Biol16, 925–31.
13.
DuncanS. A., ManovaK., ChenW. S., HoodlessP., WeinsteinD. C., BachvarovaR. F., and DarnellJ. E.Jr. (1994). Expression of transcription factor HNF-4 in the extraembryonic endoderm, gut, and nephrogenic tissue of the developing mouse embryo: HNF-4 is a marker for primary endoderm in the implanting blastocystProc Natl Acad Sci U S A91, 7598–602.
14.
DuncanS. A., NagyA., and ChanW. (1997). Murine gastrulation requires HNF-4 regulated gene expression in the visceral endoderm: tetraploid rescue of Hnf-4(-/-) embryosDevelopment124, 279–87.
15.
DurstonA. J., TimmermansJ. P., HageW. J., HendriksH. F., de VriesN. J., HeideveldM., and NieuwkoopP. D. (1989). Retinoic acid causes an anteroposterior transformation in the developing central nervous systemNature340, 140–4.
16.
FournierT., PavanL., TarradeA., SchoonjansK., AuwerxJ., Rochette-EglyC., and Evain-BrionD. (2002). The role of PPAR-γ/RXR-α heterodimers in the regulation of human trophoblast invasionAnn N Y Acad Sci973, 26–30.
17.
FuhrmannG., ChungA. C., JacksonK. J., HummelkeG., BaniahmadA., SutterJ., SylvesterI., ScholerH. R., and CooneyA. J. (2001). Mouse germline restriction of Oct4 expression by germ cell nuclear factorDev Cell1, 377–87.
18.
HihiA. K., MichalikL., and WahliW. (2002). PPARs: transcriptional effectors of fatty acids and their derivativesCell Mol Life Sci59, 790–8.
19.
HoyleC., NarvaezV., AlldusG., Lovell-BadgeR., and SwainA. (2002). Dax1 expression is dependent on steroidogenic factor 1 in the developing gonadMol Endocrinol16, 747–56.
20.
HummelkeG. C., and CooneyA. J. (2001). Germ cell nuclear factor is a transcriptional repressor essential for embryonic developmentFront Biosci6, D1186–91.
21.
IkedaY., ShenW. H., IngrahamH. A., and ParkerK. L. (1994). Developmental expression of mouse steroidogenic factor-1, an essential regulator of the steroid hydroxylasesMol Endocrinol8, 654–62.
22.
IngrahamH. A., LalaD. S., IkedaY., LuoX., ShenW. H., NachtigalM.W., AbbudR., NilsonJ. H., and ParkerK. L. (1994). The nuclear receptor steroidogenic factor 1 acts at multiple levels of the reproductive axisGenes Dev8, 2302–12.
23.
JoosT. O., DavidR., and DreyerC. (1996). xGCNF, a nuclear orphan receptor is expressed during neurulation in Xenopus laevisMech Dev60, 45–57.
24.
KamiyaA., InoueY., and GonzalezF. J. (2003). Role of the hepatocyte nuclear factor 4alpha in control of the pregnane X receptor during fetal liver developmentHepatology37, 1375–84.
25.
KastnerP., GrondonaJ. M., MarkM., GansmullerA., LeMeurM., DecimoD., VoneschJ. L., DolleP., and ChambonP. (1994). Genetic analysis of RXR α developmental function: convergence of RXR and RAR signaling pathways in heart and eye morphogenesisCell78, 987–1003.
26.
KastnerP., MarkM., and ChambonP. (1995). Nonsteroid nuclear receptors: what are genetic studies telling us about their role in real life?Cell83, 859–69.
27.
KastnerP., MarkM., GhyselinckN., KrezelW., DupeV., GrondonaJ. M., and ChambonP. (1997a). Genetic evidence that the retinoid signal is transduced by heterodimeric RXR/RAR functional units during mouse developmentDevelopment124, 313–26.
28.
KastnerP., MessaddeqN., MarkM., WendlingO., GrondonaJ. M., WardS., GhyselinckN., and ChambonP. (1997b). Vitamin A deficiency and mutations of RXRalpha, RXRbeta and RARalpha lead to early differentiation of embryonic ventricular cardiomyocytesDevelopment124, 4749–58.
29.
LohnesD., MarkM., MendelsohnC., DolleP., DierichA., GorryP., GansmullerA., and ChambonP. (1994). Function of the retinoic acid receptors (RARs) during development (I). Craniofacial and skeletal abnormalities in RAR double mutantsDevelopment120, 2723–48.
30.
LuoJ., SladekR., BaderJ. A., MatthyssenA., RossantJ., and GiguereV. (1997). Placental abnormalities in mouse embryos lacking the orphan nuclear receptor ERR-βNature388, 778–82.
31.
LuoX., IkedaY., and ParkerK. L. (1994). A cell-specific nuclear receptor is essential for adrenal and gonadal development and sexual differentiationCell77, 481–90.
32.
LuoX., IkedaY., and ParkerK. L. (1995). The cell-specific nuclear receptor steroidogenic factor 1 plays multiple roles in reproductive functionPhilos Trans R Soc Lond B Biol Sci350, 279–83.
33.
MadenM., SonneveldE., van der SaagP. T., and GaleE. (1998). The distribution of endogenous retinoic acid in the chick embryo: implications for developmental mechanismsDevelopment125, 4133–44.
34.
MangelsdorfD. J., BorgmeyerU., HeymanR. A., ZhouJ.Y., OngE. S., OroA. E., KakizukaA., and EvansR. M. (1992). Characterization of three RXR genes that mediate the action of 9-cis retinoic acidGenes Dev6, 329–44.
35.
MangelsdorfD. J., OngE. S., DyckJ. A., and EvansR. M. (1990). Nuclear receptor that identifies a novel retinoic acid response pathwayNature345, 224–9.
36.
MarillJ., IdresN., CapronC. C., NguyenE., and ChabotG. G. (2003). Retinoic acid metabolism and mechanism of action: a reviewCurr Drug Metab4, 1–10.
37.
MassaroG. D., MassaroD., and ChambonP. (2003). Retinoic acid receptor-α regulates pulmonary alveolus formation in mice after, but not during, perinatal periodAm J Physiol Lung Cell Mol Physiol284, L431–3.
38.
MattN., GhyselinckN. B., WendlingO., ChambonP., and MarkM. (2003). Retinoic acid-induced developmental defects are mediated by RARbeta/RXR heterodimers in the pharyngeal endodermDevelopment130, 2083–93.
39.
MendelsohnC., LohnesD., DecimoD., LufkinT., LeMeurM., ChambonP., and MarkM. (1994). Function of the retinoic acid receptors (RARs) during development (II). Multiple abnormalities at various stages of organogenesis in RAR double mutantsDevelopment120, 2749–71.
40.
MiquerolL., LopezS., CartierN., TulliezM., RaymondjeanM., and KahnA. (1994). Expression of the L-type pyruvate kinase gene and the hepatocyte nuclear factor 4 transcription factor in exocrine and endocrine pancreasJ Biol Chem269, 8944–51.
41.
MorriseyE. E., TangZ., SigristK., LuM. M., JiangF., IpH. S., and ParmacekM. S. (1998). GATA6 regulates HNF4 and is required for differentiation of visceral endoderm in the mouse embryoGenes Dev12, 3579–90.
42.
Morriss-KayG. M., and WardS. J. (1999). Retinoids and mammalian developmentInt Rev Cytol188, 73–131.
43.
NiederreitherK., SubbarayanV., DolleP., and ChambonP. (1999). Embryonic retinoic acid synthesis is essential for early mouse post-implantation developmentNat Genet21, 444–8.
44.
ParvizF., MatulloC., GarrisonW. D., SavatskiL., AdamsonJ. W., NingG., KaestnerK. H., RossiJ. M., ZaretK. S., and DuncanS. A. (2003). Hepatocyte nuclear factor 4alpha controls the development of a hepatic epithelium and liver morphogenesisNat Genet34, 292–6.
45.
PereiraF. A., QiuY., ZhouG., TsaiM. J., and TsaiS.Y. (1999). The orphan nuclear receptor COUP-TFII is required for angiogenesis and heart developmentGenes Dev13, 1037–49.
46.
PereiraF. A., TsaiM. J., and TsaiS.Y. (2000). COUP-TF orphan nuclear receptors in development and differentiationCell Mol Life Sci57, 1388–98.
47.
PetterssonK., SvenssonK., MattssonR., CarlssonB., OhlssonR., and BerkenstamA. (1996). Expression of a novel member of estrogen response element-binding nuclear receptors is restricted to the early stages of chorion formation during mouse embryogenesisMech Dev54, 211–23.
48.
QiuY., CooneyA. J., KurataniS., DeMayoF. J., TsaiS. Y., and TsaiM. J. (1994). Spatiotemporal expression patterns of chicken ovalbumin upstream promoter-transcription factors in the developing mouse central nervous system: evidence for a role in segmental patterning of the diencephalonProc Natl Acad Sci U S A91, 4451–5.
49.
QiuY., PereiraF. A., DeMayoF. J., LydonJ. P., TsaiS.Y., and TsaiM. J. (1997). Null mutation of mCOUP-TFI results in defects in morphogenesis of the glossopharyngeal ganglion, axonal projection, and arborizationGenes Dev11, 1925–37.
50.
RomandR., HashinoE., DolleP., VoneschJ. L., ChambonP., and GhyselinckN. B. (2002). The retinoic acid receptors RARalpha and RARgamma are required for inner ear developmentMech Dev119, 213–23.
51.
RossS. A., McCafferyP. J., DragerU. C., and De LucaL. M. (2000). Retinoids in embryonal developmentPhysiol Rev80, 1021–54.
52.
RuberteE., DolleP., ChambonP., and Morriss-KayG. (1991). Retinoic acid receptors and cellular retinoid binding proteins. II. Their differential pattern of transcription during early morphogenesis in mouse embryosDevelopment111, 45–60.
53.
RuberteE., DolleP., KrustA., ZelentA., Morriss-KayG., and ChambonP. (1990). Specific spatial and temporal distribution of retinoic acid receptor γ transcripts during mouse embryogenesisDevelopment108, 213–22.
54.
SadovskyY., CrawfordP. A., WoodsonK. G., PolishJ. A., ClementsM. A., TourtellotteL. M., SimburgerK., and MilbrandtJ. (1995). Mice deficient in the orphan receptor steroidogenic factor 1 lack adrenal glands and gonads but express P450 side-chain-cleavage enzyme in the placenta and have normal embryonic serum levels of corticosteroidsProc Natl Acad Sci U S A92, 10939–43.
55.
SagaY., KobayashiM., OhtaH., MuraiN., NakaiN., OshimaM., and TaketoM. M. (1999). Impaired extrapyramidal function caused by the targeted disruption of retinoid X receptor RXRgamma1 isoformGenes Cells4, 219–28.
56.
SchaiffW. T., CarlsonM. G., SmithS. D., LevyR., NelsonD. M., and SadovskyY. (2000). Peroxisome proliferator-activated receptor-γ modulates differentiation of human trophoblast in a ligand-specific mannerJ Clin Endocrinol Metab85, 3874–81.
57.
SchuhT. J., and KimelmanD. (1995). COUP-TFI is a potential regulator of retinoic acid-modulated development in Xenopus embryosMech Dev51, 39–49.
58.
SladekF. M., ZhongW. M., LaiE., and DarnellJ. E.Jr. (1990). Liver-enriched transcription factor HNF-4 is a novel member of the steroid hormone receptor superfamilyGenes Dev4, 2353–65.
59.
StoffelM., and DuncanS. A. (1997). The maturity-onset diabetes of the young (MODY1) transcription factor HNF4alpha regulates expression of genes required for glucose transport and metabolismProc Natl Acad Sci U S A94, 13209–14.
60.
SucovH. M., DysonE., GumeringerC. L., PriceJ., ChienK. R., and EvansR. M. (1994). RXR α mutant mice establish a genetic basis for vitamin A signaling in heart morphogenesisGenes Dev8, 1007–18.
61.
SwindellE. C., ThallerC., SockanathanS., PetkovichM., JessellT. M., and EicheleG. (1999). Complementary domains of retinoic acid production and degradation in the early chick embryoDev Biol216, 282–96.
62.
TarradeA., SchoonjansK., GuibourdencheJ., BidartJ. M., VidaudM., AuwerxJ., Rochette-EglyC., and Evain-BrionD. (2001a). PPAR γ/RXR α heterodimers are involved in human CG β synthesis and human trophoblast differentiationEndocrinology142, 4504–14.
63.
TarradeA., SchoonjansK., PavanL., AuwerxJ., Rochette-EglyC., Evain-BrionD., and FournierT. (2001b). PPARgamma/RXRalpha heterodimers control human trophoblast invasionJ Clin Endocrinol Metab86, 5017–24.
64.
ThummelC. S. (1995). From embryogenesis to metamorphosis: the regulation and function of Drosophila nuclear receptor superfamily membersCell83, 871–7.
65.
TranC. M., and SucovH. M. (1998). The RXRalpha gene functions in a non-cell-autonomous manner during mouse cardiac morphogenesisDevelopment125, 1951–6.
66.
TremblayG. B., KunathT., BergeronD., LapointeL., ChampignyC., BaderJ. A., RossantJ., and GiguereV. (2001). Diethylstilbestrol regulates trophoblast stem cell differentiation as a ligand of orphan nuclear receptor ERR βGenes Dev15, 833–8.
67.
WendlingO., GhyselinckN. B., ChambonP., and MarkM. (2001). Roles of retinoic acid receptors in early embryonic morphogenesis and hindbrain patterningDevelopment128, 2031–8.
68.
WilhelmD., and EnglertC. (2002). The Wilms tumor suppressor WT1 regulates early gonad development by activation of Sf1Genes Dev16, 1839–51.
69.
ZhouC., TsaiS. Y., and TsaiM. J. (2001). COUP-TFI: an intrinsic factor for early regionalization of the neocortexGenes Dev15, 2054–9.
70.
ZileM. H. (2001). Function of vitamin A in vertebrate embryonic developmentJ Nutr131, 705–8.