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.
???displayArticle.abstract???
The administration of the teratogen retinoic acid (and other retinoids) to vertebrate embryos causes a range of developmental abnormalities. It remains to be shown how these teratogenic effects are mediated, and whether or not they reflect any morphogenetic roles retinoids may have in normal development. The most intensively studied cellular action of retinoids has been the activation of retinoid receptors (RARs and RXRs), which are members of the steroid/thyroid family of ligand-modulated transcription factors. Here we report experiments designed to investigate whether the teratogenic effects of retinoic acid on early Xenopus embryos are mediated transcriptionally by receptors, and if these receptors are necessary for normal early Xenopus development. We have demonstrated transcriptional activation of injected reporter genes by exogeneously supplied retinoic acid in Xenopus embryos, presumably as a consequence of the activation of endogenous retinoid receptors. This assay system has been used to demonstrate functional expression, from injected mRNA of (1) a wild-type RARγ (2) a domain-swapped receptor in which the retinoic acid binding domain has been replaced by a thyroid hormone domain to create a thyroid hormone responsive receptor, and (3) a dominant negative from of the RARγ. The wild-type RARγ increases the severity of retinoic acid-mediated defects. In the presence of thyroid hormone the domain-swapped receptor causes abnormalities of gastrulation. The dominant negative decreases the severity of retinoic acid-mediated defects. We conclude that the teratogenic effects of exogenous retinoic acid on Xenopus embryos are mediated, at least in part, transcriptionally via retinoid receptors. It is notable that the dominant negative has no effect on normal development in the absence of exogenous retinoic acid. This is despite observations that this receptor completely blocks transcriptional activation of reporter genes by exogenous retinoic acid up to the beginning of gastrulation, and substantially relieves the teratogenic effects of retinoic acid.
Amaya,
Expression of a dominant negative mutant of the FGF receptor disrupts mesoderm formation in Xenopus embryos.
1991, Pubmed,
Xenbase
Amaya,
Expression of a dominant negative mutant of the FGF receptor disrupts mesoderm formation in Xenopus embryos.
1991,
Pubmed
,
Xenbase
Balling,
CRABP and the teratogenic effects of retinoids.
1991,
Pubmed
Bernard,
Retinoic acid alters the proportion of high mannose to complex type oligosaccharides on fibronectin secreted by cultured chondrocytes.
1984,
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
Bolmer,
Retinoids and phorbol esters alter release of fibronectin from enucleated cells.
1982,
Pubmed
Brent,
Mutations of the rat growth hormone promoter which increase and decrease response to thyroid hormone define a consensus thyroid hormone response element.
1989,
Pubmed
Brooks,
Structure and functional expression of a cloned Xenopus thyroid hormone receptor.
1989,
Pubmed
,
Xenbase
Cho,
Differential activation of Xenopus homeo box genes by mesoderm-inducing growth factors and retinoic acid.
1990,
Pubmed
,
Xenbase
Cho,
Overexpression of a homeodomain protein confers axis-forming activity to uncommitted Xenopus embryonic cells.
1991,
Pubmed
,
Xenbase
De Luca,
The direct involvement of vitamin A in glycosyl transfer reactions of mammalian membranes.
1977,
Pubmed
de Thé,
Identification of a retinoic acid responsive element in the retinoic acid receptor beta gene.
1990,
Pubmed
DINGLE,
VITAMIN A, CAROTENOIDS AND CELL FUNCTION.
1965,
Pubmed
Dollé,
Retinoic acid receptors and cellular retinoid binding proteins. I. A systematic study of their differential pattern of transcription during mouse organogenesis.
1990,
Pubmed
Durston,
Retinoic acid causes an anteroposterior transformation in the developing central nervous system.
1989,
Pubmed
,
Xenbase
Ellinger-Ziegelbauer,
A retinoic acid receptor expressed in the early development of Xenopus laevis.
1991,
Pubmed
,
Xenbase
Giguere,
Identification of a receptor for the morphogen retinoic acid.
,
Pubmed
Giguère,
Identification of a novel isoform of the retinoic acid receptor gamma expressed in the mouse embryo.
1990,
Pubmed
Glass,
Positive and negative regulation of gene transcription by a retinoic acid-thyroid hormone receptor heterodimer.
1989,
Pubmed
Glass,
Multiple cell type-specific proteins differentially regulate target sequence recognition by the alpha retinoic acid receptor.
1990,
Pubmed
Gorman,
Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells.
1982,
Pubmed
Green,
Nuclear hormone receptors. Promiscuous liaisons.
1993,
Pubmed
Heyman,
9-cis retinoic acid is a high affinity ligand for the retinoid X receptor.
1992,
Pubmed
Horton,
Engineering hybrid genes without the use of restriction enzymes: gene splicing by overlap extension.
1989,
Pubmed
Jones,
Development of the ectoderm in Xenopus: tissue specification and the role of cell association and division.
1986,
Pubmed
,
Xenbase
Kastner,
Murine isoforms of retinoic acid receptor gamma with specific patterns of expression.
1990,
Pubmed
Kliewer,
Retinoid X receptor interacts with nuclear receptors in retinoic acid, thyroid hormone and vitamin D3 signalling.
1992,
Pubmed
Krieg,
Functional messenger RNAs are produced by SP6 in vitro transcription of cloned cDNAs.
1984,
Pubmed
,
Xenbase
Krust,
A third human retinoic acid receptor, hRAR-gamma.
1989,
Pubmed
Leid,
Multiplicity generates diversity in the retinoic acid signalling pathways.
1992,
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
Lohnes,
Function of retinoic acid receptor gamma in the mouse.
1993,
Pubmed
Mangelsdorf,
Characterization of three RXR genes that mediate the action of 9-cis retinoic acid.
1992,
Pubmed
Mavilio,
Regulation of vertebrate homeobox-containing genes by morphogens.
1993,
Pubmed
Old,
Precocious synthesis of a thyroid hormone receptor inXenopus embryos causes hormone-dependent developmental abnormalities.
1992,
Pubmed
,
Xenbase
Petkovich,
A human retinoic acid receptor which belongs to the family of nuclear receptors.
,
Pubmed
Ragsdale,
Identification of a novel retinoic acid receptor in regenerative tissues of the newt.
1989,
Pubmed
Richter,
Gene expression in the embryonic nervous system of Xenopus laevis.
1988,
Pubmed
,
Xenbase
Ruberte,
Retinoic acid receptors and cellular retinoid binding proteins. II. Their differential pattern of transcription during early morphogenesis in mouse embryos.
1991,
Pubmed
Ruiz i Altaba,
Retinoic acid modifies the pattern of cell differentiation in the central nervous system of neurula stage Xenopus embryos.
1991,
Pubmed
,
Xenbase
Ruiz i Altaba,
Retinoic acid modifies mesodermal patterning in early Xenopus embryos.
1991,
Pubmed
,
Xenbase
Sharpe,
Retinoic acid can mimic endogenous signals involved in transformation of the Xenopus nervous system.
1991,
Pubmed
,
Xenbase
Shen,
Dominant negative retinoic acid receptor beta.
1993,
Pubmed
Sive,
Retinoic acid perturbs the expression of Xhox.lab genes and alters mesodermal determination in Xenopus laevis.
1991,
Pubmed
,
Xenbase
Sive,
Identification of a retinoic acid-sensitive period during primary axis formation in Xenopus laevis.
1990,
Pubmed
,
Xenbase
Sweeney,
Trans-activation of transcription, from promoters containing immunoglobulin gene octamer sequences, by myeloma cell mRNA in Xenopus oocytes.
1988,
Pubmed
,
Xenbase
Thomas,
Heterodimerization of the Drosophila ecdysone receptor with retinoid X receptor and ultraspiracle.
1993,
Pubmed
Umesono,
Retinoic acid and thyroid hormone induce gene expression through a common responsive element.
1988,
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
Zelent,
Cloning of murine alpha and beta retinoic acid receptors and a novel receptor gamma predominantly expressed in skin.
1989,
Pubmed
Zerlauth,
Kinetics of fibronectin release from fibroblasts in response to 12-O-tetradecanoylphorbol-13-acetate and retinoic acid.
1984,
Pubmed
Zhang,
Retinoid X receptor is an auxiliary protein for thyroid hormone and retinoic acid receptors.
1992,
Pubmed
