Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Mol Cell Biol
1997 Aug 01;178:4738-49. doi: 10.1128/MCB.17.8.4738.
Show Gene links
Show Anatomy links
Both thyroid hormone and 9-cis retinoic acid receptors are required to efficiently mediate the effects of thyroid hormone on embryonic development and specific gene regulation in Xenopus laevis.
???displayArticle.abstract???
Tissue culture transfection and in vitro biochemical studies have suggested that heterodimers of thyroid hormone receptors (TRs) and 9-cis retinoic acid receptors (RXRs) are the likely in vivo complexes that mediate the biological effects of thyroid hormone, 3,5,3'-triiodothyronine (T3). However, direct in vivo evidence for such a hypothesis has been lacking. We have previously reported a close correlation between the coordinated expression of TR and RXR genes and tissue-dependent temporal regulation of organ transformations during Xenopus laevis metamorphosis. By introducing TRs and RXRs either individually or together into developing Xenopus embryos, we demonstrate here that RXRs are critical for the developmental function of TRs. Precocious expression of TRs and RXRs together but not individually leads to drastic, distinct embryonic abnormalities, depending upon the presence or absence of T3, and these developmental effects require the same receptor domains as those required for transcriptional regulation by TR-RXR heterodimers. More importantly, the overexpressed TR-RXR heterodimers faithfully regulate endogenous T3 response genes that are normally regulated by T3 only during metamorphosis. That is, they repress the genes in the absence of T3 and activate them in the presence of the hormone. On the other hand, the receptors have no effect on a retinoic acid (RA) response gene. Thus, RA- and T3 receptor-mediated teratogenic effects in Xenopus embryos occur through distinct molecular pathways, even though the resulting phenotypes have similarities.
FIG. 2. Overexpression of TRs and RXRs together results in dose- and T3-dependent embryonic abnormalities. Embryos were injected with the indicated amounts of TR-RXR mRNAs and cultured for 2 days in the presence (ï°) or absence (ï²) of 100 nM T3.
FIG. 7. Phenotypic analyses of the embryos injected with wild-type and mutant receptor mRNAs reveal that the requirements for receptor function in embryo- genesis and transcriptional regulation in oocytes are identical. The embryos injected with indicated mRNAs were cultured in the presence (B, D, F, and H) or absence (A, C, E, and G) of T3, and their phenotypes were examined after 48 h. Comparisons of TRalphaA and TRbetaA (A and B), TRalphaA and and TBetaADeltaAF2 (C and D), TRalpha and TRalphaADeltaDBD (E and F), and RXRaplha and RXRalphaDeltaAF2 (G and H) are shown. Note that the phenotypes of embryos with over-expressed TRBetaalphaAF2-RXR in the presence of T3 were identical to those in the absence of T3.
Baniahmad,
Enhancement of human estrogen receptor activity by SPT6: a potential coactivator.
1995, Pubmed
Baniahmad,
Enhancement of human estrogen receptor activity by SPT6: a potential coactivator.
1995,
Pubmed
Baniahmad,
A transferable silencing domain is present in the thyroid hormone receptor, in the v-erbA oncogene product and in the retinoic acid receptor.
1992,
Pubmed
Banker,
The thyroid hormone receptor gene (c-erbA alpha) is expressed in advance of thyroid gland maturation during the early embryonic development of Xenopus laevis.
1991,
Pubmed
,
Xenbase
Banker,
Thyroid hormone receptor can modulate retinoic acid-mediated axis formation in frog embryogenesis.
1993,
Pubmed
,
Xenbase
Basset,
A novel metalloproteinase gene specifically expressed in stromal cells of breast carcinomas.
,
Pubmed
Blumberg,
Multiple retinoid-responsive receptors in a single cell: families of retinoid "X" receptors and retinoic acid receptors in the Xenopus egg.
1992,
Pubmed
,
Xenbase
Brent,
Thyroid hormone aporeceptor represses T3-inducible promoters and blocks activity of the retinoic acid receptor.
1989,
Pubmed
Brown,
The thyroid hormone-induced tail resorption program during Xenopus laevis metamorphosis.
1996,
Pubmed
,
Xenbase
Bumcrot,
Somite differentiation. Sonic signals somites.
1995,
Pubmed
Chakravarti,
Role of CBP/P300 in nuclear receptor signalling.
1996,
Pubmed
Chen,
A transcriptional co-repressor that interacts with nuclear hormone receptors.
1995,
Pubmed
Durston,
Retinoic acid causes an anteroposterior transformation in the developing central nervous system.
1989,
Pubmed
,
Xenbase
Eliceiri,
Quantitation of endogenous thyroid hormone receptors alpha and beta during embryogenesis and metamorphosis in Xenopus laevis.
1994,
Pubmed
,
Xenbase
Evans,
The steroid and thyroid hormone receptor superfamily.
1988,
Pubmed
Forman,
Interactions among a subfamily of nuclear hormone receptors: the regulatory zipper model.
1990,
Pubmed
Glass,
Positive and negative regulation of gene transcription by a retinoic acid-thyroid hormone receptor heterodimer.
1989,
Pubmed
Graupner,
Dual regulatory role for thyroid-hormone receptors allows control of retinoic-acid receptor activity.
1989,
Pubmed
Halachmi,
Estrogen receptor-associated proteins: possible mediators of hormone-induced transcription.
1994,
Pubmed
Helbing,
Sequential up-regulation of thyroid hormone beta receptor, ornithine transcarbamylase, and carbamyl phosphate synthetase mRNAs in the liver of Rana catesbeiana tadpoles during spontaneous and thyroid hormone-induced metamorphosis.
1992,
Pubmed
,
Xenbase
Herrin,
Rapid, reversible staining of northern blots prior to hybridization.
1988,
Pubmed
Heyman,
9-cis retinoic acid is a high affinity ligand for the retinoid X receptor.
1992,
Pubmed
Hörlein,
Ligand-independent repression by the thyroid hormone receptor mediated by a nuclear receptor co-repressor.
1995,
Pubmed
Hunter,
Retinoic acid stimulates neurite outgrowth in the amphibian spinal cord.
1991,
Pubmed
Ishizuya-Oka,
Transient expression of stromelysin-3 mRNA in the amphibian small intestine during metamorphosis.
1996,
Pubmed
,
Xenbase
Kawahara,
Developmental and regional expression of thyroid hormone receptor genes during Xenopus metamorphosis.
1991,
Pubmed
,
Xenbase
Kim,
In vivo genomic footprinting of thyroid hormone-responsive genes in pituitary tumor cell lines.
1996,
Pubmed
Kraft,
The retinoid X receptor ligand, 9-cis-retinoic acid, is a potential regulator of early Xenopus development.
1994,
Pubmed
,
Xenbase
Kurokawa,
Differential orientations of the DNA-binding domain and carboxy-terminal dimerization interface regulate binding site selection by nuclear receptor heterodimers.
1993,
Pubmed
Le Douarin,
The N-terminal part of TIF1, a putative mediator of the ligand-dependent activation function (AF-2) of nuclear receptors, is fused to B-raf in the oncogenic protein T18.
1995,
Pubmed
Lee,
Two classes of proteins dependent on either the presence or absence of thyroid hormone for interaction with the thyroid hormone receptor.
1995,
Pubmed
Lee,
Interaction of thyroid-hormone receptor with a conserved transcriptional mediator.
1995,
Pubmed
Leid,
Purification, cloning, and RXR identity of the HeLa cell factor with which RAR or TR heterodimerizes to bind target sequences efficiently.
1992,
Pubmed
Machuca,
Analysis of structure and expression of the Xenopus thyroid hormone receptor-beta gene to explain its autoinduction.
1995,
Pubmed
,
Xenbase
Mangelsdorf,
The nuclear receptor superfamily: the second decade.
1995,
Pubmed
Marks,
H-2RIIBP (RXR beta) heterodimerization provides a mechanism for combinatorial diversity in the regulation of retinoic acid and thyroid hormone responsive genes.
1992,
Pubmed
Minucci,
Retinoid X receptor-selective ligands produce malformations in Xenopus embryos.
1996,
Pubmed
,
Xenbase
Oñate,
Sequence and characterization of a coactivator for the steroid hormone receptor superfamily.
1995,
Pubmed
Papalopulu,
Retinoic acid causes abnormal development and segmental patterning of the anterior hindbrain in Xenopus embryos.
1991,
Pubmed
,
Xenbase
Patterton,
Transcriptional activation of the matrix metalloproteinase gene stromelysin-3 coincides with thyroid hormone-induced cell death during frog metamorphosis.
1995,
Pubmed
,
Xenbase
Perlman,
Thyroid hormone nuclear receptor. Evidence for multimeric organization in chromatin.
1982,
Pubmed
Perlmann,
Determinants for selective RAR and TR recognition of direct repeat HREs.
1993,
Pubmed
Perrimon,
Hedgehog and beyond.
1995,
Pubmed
Puzianowska-Kuznicka,
Nuclear factor I as a potential regulator during postembryonic organ development.
1996,
Pubmed
,
Xenbase
Ranjan,
Transcriptional repression of Xenopus TR beta gene is mediated by a thyroid hormone response element located near the start site.
1994,
Pubmed
,
Xenbase
Ruiz i Altaba,
Retinoic acid modifies mesodermal patterning in early Xenopus embryos.
1991,
Pubmed
,
Xenbase
Ruiz i Altaba,
Retinoic acid modifies the pattern of cell differentiation in the central nervous system of neurula stage Xenopus embryos.
1991,
Pubmed
,
Xenbase
Sap,
The c-erb-A protein is a high-affinity receptor for thyroid hormone.
,
Pubmed
Sap,
Repression of transcription mediated at a thyroid hormone response element by the v-erb-A oncogene product.
1989,
Pubmed
Schneider,
Regulation of c-erbA-alpha messenger RNA species in tadpole erythrocytes by thyroid hormone.
1991,
Pubmed
,
Xenbase
Shi,
Thyroid Hormone Receptors: Mechanisms of Transcriptional Regulation and Roles during Frog Development.
1996,
Pubmed
Shi,
Tadpole competence and tissue-specific temporal regulation of amphibian metamorphosis: roles of thyroid hormone and its receptors.
1996,
Pubmed
,
Xenbase
Shi,
Tissue-dependent developmental expression of a cytosolic thyroid hormone protein gene in Xenopus: its role in the regulation of amphibian metamorphosis.
1994,
Pubmed
,
Xenbase
Shi,
Biphasic intestinal development in amphibians: embryogenesis and remodeling during metamorphosis.
1996,
Pubmed
,
Xenbase
Sive,
Identification of a retinoic acid-sensitive period during primary axis formation in Xenopus laevis.
1990,
Pubmed
,
Xenbase
Stolow,
Xenopus sonic hedgehog as a potential morphogen during embryogenesis and thyroid hormone-dependent metamorphosis.
1995,
Pubmed
,
Xenbase
Tata,
Gene expression during metamorphosis: an ideal model for post-embryonic development.
1993,
Pubmed
Tsai,
Molecular mechanisms of action of steroid/thyroid receptor superfamily members.
1994,
Pubmed
Ulisse,
Dominant-negative mutant thyroid hormone receptors prevent transcription from Xenopus thyroid hormone receptor beta gene promoter in response to thyroid hormone in Xenopus tadpoles in vivo.
1996,
Pubmed
,
Xenbase
Wang,
Thyroid hormone-induced gene expression program for amphibian tail resorption.
1993,
Pubmed
,
Xenbase
Weinberger,
The c-erb-A gene encodes a thyroid hormone receptor.
,
Pubmed
Wong,
Coordinated regulation of and transcriptional activation by Xenopus thyroid hormone and retinoid X receptors.
1995,
Pubmed
,
Xenbase
Wong,
A role for nucleosome assembly in both silencing and activation of the Xenopus TR beta A gene by the thyroid hormone receptor.
1995,
Pubmed
,
Xenbase
Yaoita,
Xenopus laevis alpha and beta thyroid hormone receptors.
1990,
Pubmed
,
Xenbase
Yaoita,
A correlation of thyroid hormone receptor gene expression with amphibian metamorphosis.
1990,
Pubmed
,
Xenbase
Yoshizato,
Biochemistry and cell biology of amphibian metamorphosis with a special emphasis on the mechanism of removal of larval organs.
1989,
Pubmed
Yu,
RXR beta: a coregulator that enhances binding of retinoic acid, thyroid hormone, and vitamin D receptors to their cognate response elements.
1991,
Pubmed
Zhang,
Retinoid X receptor is an auxiliary protein for thyroid hormone and retinoic acid receptors.
1992,
Pubmed
