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O Destrée

Publications and source records attributed to O Destrée.

16 recordsLinked to original sources
PubMed2001

Expression of Tcf/Lef and sFrp and localization of beta-catenin in the developing mouse lung.

Recent evidence that Wnts and other genes in the Wnt signaling pathway are expressed in embryonic and adult mouse lung suggests that this pathway is important for cell fate decisions and differentiation of lung cell types. We therefore examined the expression and protein distribution of several Wnt pathway components during prenatal mouse lung development using whole-mount in situ hybridization and immunohistochemistry. Between embryonic days 10.5 and 17.5 (E10.5-E17.5), beta-catenin was localized in the cytoplasm, and often also the nucleus, of the undifferentiated primordial epithelium (PE), differentiating alveolar epithelium (AE; present from E14.5 onward), and adjacent mesenchyme. Tcf1, Lef1, Tcf3, Tcf4, sFrp1, sFrp2 and sFrp4 were also expressed in the PE, AE, and adjacent mesenchyme in specific spatio-temporal patterns.

Animals↗
PubMed2000

Protection against oxidative damage by iron chelators: effect of lipophilic analogues and prodrugs of N,N'-bis(3,4,5-trimethoxybenzyl)ethylenediamine- N,N'-diacetic acid (OR10141).

N,N'-Bis(3,4,5-trimethoxybenzyl)ethylenediamine-N,N'-diacetic acid (1) was recently described as a new type of iron chelator for protection against oxidative damage. It has a low affinity for iron, but the corresponding iron complex undergoes a site-specific oxidation by hydrogen peroxide through intramolecular aromatic hydroxylation into a highly stable iron phenolato complex, which does not catalyze hydroxyl radical formation. The purpose of this local activation process is to minimize toxicity compared to strong iron chelators, which may interfere with normal iron metabolism. 1 efficiently protects biological molecules against oxidative damage in vitro but not intact cells because of poor membrane permeability. We show here that, among a series of prodrug esters and lipophilic analogues, membrane-permeant N,N'-bis(3,4,5-trimethoxybenzyl)ethylenediamine-N,N'-diacetic acid diacetoxymethyl ester (7) protects human skin fibroblasts against hydrogen peroxide toxicity with an IC(50) of 3 microM. These results thus demonstrate that, providing sufficient intracellular chelator concentration is reached, 1 efficiently protects cells against the deleterious effects of hydrogen peroxide. This strategy of oxidative activation should help the design of new chelators with better safety margins, which may be useful against oxidative damage under conditions where a prolonged administration is needed.

Antioxidants↗
PubMed2000

Differential expression of the Groucho-related genes 4 and 5 during early development of Xenopus laevis.

Recently, we demonstrated that the Xenopus Wnt effector XTcf-3 interacts with Groucho-related transcriptional repressors (Roose et al., 1998. Nature 395, 608-612). A long form of the Groucho-related genes, XGrg-4, was shown to repress axis formation in the Xenopus embryo, whereas a short form, XGrg-5, acted as a potentiator. In this study, the temporal and spatial expression of XGrg-4 and XGrg-5 is described in Xenopus laevis embryos. Both genes are maternally expressed. In the gastrula, transcripts of both genes are present in the animal as well as the vegetal region. At later stages, XGrg-4 and XGrg-5 show specific patterns of expression in the central nervous system (CNS), cranial ganglia, eyes, otic vesicles, stomodeal-hypophyseal anlage, cement gland, head mesenchyme, branchial arches, neural crest and derivatives, somites, pronephros, pronephric duct, heart and tailbud. Differences in the expression of XGrg-4 and XGrg-5 were found in the CNS, cranial ganglia, olfactory placodes, stomodeal-pharyngeal anlage, cement gland, head mesenchyme and ectoderm.

Animals↗
PubMed1999

Identification of APC2, a homologue of the adenomatous polyposis coli tumour suppressor.

The adenomatous polyposis coli (APC) tumour-suppressor protein controls the Wnt signalling pathway by forming a complex with glycogen synthase kinase 3beta (GSK-3beta), axin/conductin and betacatenin. Complex formation induces the rapid degradation of betacatenin. In colon carcinoma cells, loss of APC leads to the accumulation of betacatenin in the nucleus, where it binds to and activates the Tcf-4 transcription factor (reviewed in [1] [2]). Here, we report the identification and genomic structure of APC homologues. Mammalian APC2, which closely resembles APC in overall domain structure, was functionally analyzed and shown to contain two SAMP domains, both of which are required for binding to conductin. Like APC, APC2 regulates the formation of active betacatenin-Tcf complexes, as demonstrated using transient transcriptional activation assays in APC -/- colon carcinoma cells. Human APC2 maps to chromosome 19p13.3. APC and APC2 may therefore have comparable functions in development and cancer.

Adenomatous Polyposis Coli↗
PubMed1999

In vivo analysis of Frat1 deficiency suggests compensatory activity of Frat3.

The Frat1 gene was first identified as a proto-oncogene involved in progression of mouse T cell lymphomas. More recently, FRAT/GBP (GSK-3beta Binding Protein) family members have been recognized as critical components of the Wnt signal transduction pathway. In an attempt to gain more insight into the function of Frat1, we have generated Frat1-deficient mice in which most of the coding domain was replaced by a promoterless beta-galactosidase reporter gene. While the pattern of LacZ expression in Frat1(lacZ)/+ mice indicated Frat1 to be expressed in various neural and epithelial tissues, homozygous Frat1(lacZ) mice were apparently normal, healthy and fertile. Tissues of homozygous Frat1(lacZ) mice showed expression of a second mouse Frat gene, designated Frat3. The Frat1 and Frat3 proteins are structurally and functionally very similar, since both Frat1 and Frat3 are capable of inducing a secondary axis in Xenopus embryos. The overlapping expression patterns of Frat1 and Frat3 during murine embryogenesis suggest that the apparent dispensability of Frat1 for proper development may be due to the presence of a second mouse gene encoding a functional Frat protein.

Adaptor Proteins, Signal Transducing↗
PubMed1999

A tight control over Wnt action.

Here, we review the WNT pathway and its regulation at different levels. We focus on the transcriptional regulation of WNT target genes, in light of the recently identified negative regulators, i.e. relatives of groucho and CBP.

Animals↗
PubMed1998

Protection of U937 cells against oxidative injury by a novel series of iron chelators.

A new series of iron chelators designed to protect tissues against iron-catalysed oxidative damage is described. These compounds are aminocarboxylate derivatives bearing pendant aromatic groups. They were designed to have a relatively low affinity for both ferrous and ferric iron and to be site-specifically oxidizable by hydrogen peroxide through intramolecular aromatic hydroxylation into species with strong iron binding capacity which do not catalyse hydroxyl radical formation. Thus, at the cellular level, oxidative injury is used to convert weak iron chelators into strong iron chelators in order to promote cell survival. The purpose of this local activation process is to minimise toxicity compared to strong iron chelators which may interfere with normal iron metabolism. Compounds within this series were evaluated in vitro in view of their capacity to undergo intramolecular hydroxylation and to protect cultured cells against oxidative injury. Results show that the intramolecular aromatic hydroxylation capacity is critically dependent upon the amino carboxylate chelating moieties and the substituents of the aromatic rings. Cell protection against oxidative injury is only observed with compounds possessing sufficient lipophilicity. The monohydroxylation product of N,N'-dibenzylethylenediamine N,N'-diacetic acid, protects cells against both H2O2 and tBuOOH toxicity with IC50's of 12 and 60 microM, respectively, in agreement with the oxidative activation concept. These results represent the first step toward the development of a new strategy to safe iron chelation for the prevention of oxidative damage.

Ascorbic Acid↗
PubMed1998

The Xenopus Wnt effector XTcf-3 interacts with Groucho-related transcriptional repressors.

Tcf/Lef transcription factors mediate signalling from Wingless/Wnt proteins by recruiting Armadillo/beta-catenin as a transcriptional co-activator. However, studies of Drosophila, Xenopus and Caenorhabditis elegans have indicated that Tcf factors may also be transcriptional repressors. Here we show that Tcf factors physically interact with members of the Groucho family of transcriptional repressors. In transient transfection assays, the Xenopus Groucho homologue XGrg-4 inhibited activation of transcription of synthetic Tcf reporter genes. In contrast, the naturally truncated Groucho-family member XGrg-5 enhanced transcriptional activation. Injection of XGrg-4 into Xenopus embryos repressed transcription of Siamois and Xnr-3, endogenous targets of beta-catenin-Tcf. Dorsal injection of XGrg-4 had a ventralizing effect on Xenopus embryos. Secondary-axis formation induced by a dominant-positive Armadillo-Tcf fusion protein was inhibited by XGrg-4 and enhanced by XGrg-5. These data indicate that expression of Tcf target genes is regulated by a balance between Armadillo and Groucho.

Animals↗
PubMed1998

Differential expression of the HMG box transcription factors XTcf-3 and XLef-1 during early xenopus development.

The recent discovery that the HMG box transcription factor XTCF-3 is involved in early axis specification in Xenopus laevis (Molenaar, M., van de Wetering, M., Oosterwegel, M., Peterson-Maduro, J. Godsave, S., Korinek, V., Roose, J., Destree, O., Clevers, H., 1996. XTcf-3 transcription factor mediates beta-catenin-induced axis formation in Xenopus embryos. Cell 86, 391-399) led us to search for other members of the TCF/LEF family in this species. A newly identified HMG box factor was cloned with highest homology to human LEF-1, called XLEF-1. Unlike XTcf-3, XLef-1 is not expressed maternally, but its transcripts become detectable directly after the mid blastula transition (MBT). At later stages, both genes are expressed in the central nervous system (CNS), eyes, otic vesicles, head mesenchyme, neural crest and derivatives, branchial arches, developing heart, tailbud and limb buds. The expression pattern of Lef-1 during later stages of development is evolutionarily conserved.

Amino Acid Sequence↗
PubMed1996

XTcf-3 transcription factor mediates beta-catenin-induced axis formation in Xenopus embryos.

XTcf-3 is a maternally expressed Xenopus homolog of the mammalian HMG box factors Tcf-1 and Lef-1. The N-terminus of XTcf-3 binds to beta-catenin. Microinjection of XTcf-3 mRNA in embryos results in nuclear translocation of beta-catenin. The beta-catenin-XTcf-3 complex activates transcription in a transient reporter gene assay, while XTcf-3 by itself is silent. N-terminal deletion of XTcf-3 (delta N) abrogates the interaction with beta-catenin, as well as the consequent transcription activation. This dominant-negative delta N mutant suppresses the induction of axis duplication by microinjected beta-catenin. It also suppresses endogenous axis specification upon injection into the dorsal blastomeres of a 4-cell-stage embryo. We propose that signaling by beta-catenin involves complex formation with XTcf-3, followed by nuclear translocation and activation of specific XTcf-3 target genes.

Amino Acid Sequence↗
PubMed1989

Isolation of the Xenopus homolog of int-1/wingless and expression during neurula stages of early development.

We have isolated the Xenopus homolog (Xint-1) of the mouse protooncogene int-1 from a neurula stage 17 cDNA library. The deduced protein sequence of Xint-1 includes 371 amino acids. The Xint-1 protein is more similar to the mammalian int-1 product (69%), than to the Drosophila counterpart of int-1, wingless (50%). Xint-1 shares several characteristics of secreted proteins with the other int-1 homologs: it has a hydrophobic leader, multiple conserved potential N-linked glycosylation sites and is rich in cysteine residues. All 23 cysteines are conserved in the three proteins. Xint-1 is transiently expressed during the neurula stages of early Xenopus development.

Amino Acid Sequence↗
PubMed1987

A mouse homeobox containing gene on chromosome 11: sequence and tissue-specific expression.

We have molecularly cloned a mouse homeobox containing gene by isolating cDNA and genomic clones. The gene is located in a previously described cluster on chromosome 11 (Hart et al. (1985) Cell 43, 9-18) and was identified as the Hox2.3 gene. We present the complete mRNA sequence of this gene and describe similarities to other homeobox containing genes, among which its human homologue, the cl gene. High expression of the Hox2.3 gene was found in kidney, testis, and spinal cord of adult mice, in the spinal cord of 12.5-17.5 day embryos and in differentiating EC cells depending on their treatment. Three different treatments of the pluripotent EC cell line P19, each leading to the induction of a specific differentiation pathway, resulted in all cases in induction of Hox2.3; however, major quantitative differences in this response were observed.

Amino Acid Sequence↗
PubMed1987

Abundant expression of homeobox genes in mouse embryonal carcinoma cells correlates with chemically induced differentiation.

Mammalian homeobox-containing genes might play a role in embryonal pattern formation. In favor of this view is the recently reported expression of such genes during mouse embryogenesis [Manley, J. L. & Levine, M. S. (1985) Cell 43, 1-2]. The embryo-derived stem cells and in particular the pluripotent embryonal carcinoma (EC) cell lines are generally considered as a valid model of early mouse development. Homeobox-containing genes were shown to be expressed in differentiating EC cells. We have analyzed the expression of several of these genes in three EC cell lines triggered to differentiate by alternative treatments in the presence or in the absence of retinoic acid. In both types of conditions, C17S1 (clone 1003) and PCC7.S Aza R1 EC cells were induced to differentiate into mainly neurones, and PSA-1 EC cells were induced to differentiate into a large spectrum of tissue derivatives. Induction to high levels of expression of several homeobox-containing genes during differentiation occurs only in the presence of retinoic acid. Nonchemical treatment triggering differentiation does not lead to detectable expression of these genes. Accumulation to high amounts of homeobox-containing gene transcripts in these experiments seems to correlate with retinoic acid-induced EC cell differentiation rather than with EC cell differentiation as such.

Animals↗
PubMed1987

The mouse Hox2.3 homeobox-containing gene: regulation in differentiating pluripotent stem cells and expression pattern in embryos.

Genomic and cDNA clones of the mouse Hox2.3 gene have been isolated. Expression of this gene was characterized in differentiating embryonal carcinoma (EC) and embryonic stem (ES) cells, and in the 13.5-day embryo. Hox2.3 is expressed at a very low level, if at all, in undifferentiated ES and EC cells. As previously reported for the Hox1.1 and Hox2.1 genes, differentiation of pluripotent stem cells induced by a nonchemical method is not accompanied by strong accumulation of Hox2.3 transcripts. Treatment of the stem cells with a chemical inducer like retinoic acid (RA), and also hexamethylenebisacetamide (HMBA), or 5-bromo-2'-deoxyuridine (BUdR), simultaneously accelerates differentiation and stimulates accumulation of Hox2.3 mRNA to high levels. Addition of RA several days after the cells have been induced to differentiate by a nonchemical method induces Hox2.3-transcript accumulation as well. For comparison, expression of the En-1 gene, which contains a homeobox belonging to a different class from that of the Antennapedia-related Hox1.1, Hox2.1, and Hox2.3 genes, was analyzed. The En-1 gene was found also to be sensitive to this regulation by chemical inducers of differentiation. It was observed that treatment of undifferentiated EC cells with the inhibitor of protein synthesis cycloheximide resulted in slight accumulation of Hox2.3 mRNA, suggesting the involvement of a short-lived protein in keeping the level of homeobox-gene transcription low in EC cells. The highest level of Hox2.3 transcripts in 13.5-day embryos in vivo was observed in the spinal cord. Comparison with the expression pattern of three other homeobox genes revealed overlapping gradients of mRNA along the longitudinal brain-spinal-cord axis. An important question is that of the molecular basis for such a spatially restricted accumulation of homeobox transcripts. Hox2.3 is expressed at a much lower level in rat and mouse embryonic midbrain than in spinal cord in vivo. We have shown that addition of RA to primary cultures of cells from rat embryo mesencephalon leads to strong accumulation of Hox2.3 mRNA. A possible interpretation is that RA mimics one or more spatially restricted effectors, accounting for the local accumulation of Hox2.3 transcripts in the embryonic central nervous system. Control of Hox2.3 gene expression in vivo may obey some similar mechanisms as in chemically stimulated EC and ES cells in vitro.

Acetamides↗
PubMed1981

The organization of the histone genes in the genome of Xenopus laevis.

We have studied the organization of the histone genes in the DNA from several individuals of Xenopus laevis. For that purpose, Southern blots of genomic DNA, that was digested with several restriction enzymes, were hybridized with radioactively labeled DNA fragments from clone X1-hi-1 (14), containing genes for Xenopus histones H2A, H2B, H3 and H4. In the DNA of all animals that were screened we found a major repeating unit of 14 kilobasepairs, which contains genes for histones H2A, H2B, H3 and H4 (H1 not tested) and is represented up to 30 times in the genome. The order of the genes in this major repeating unit is H4 - H3 - H2A - H2B. This order is different from that in the histone DNA of clone X1-hi-1, i.e. H3 - H4 - H2A - H2B. In addition to the genes in the major repeating unit, histone genes are present in unique restriction fragments in numbers that vary from one animal to another. The restriction patterns for the histone genes in these unique fragments were found to be different for all eight Xenopus individuals that were screened. The cloned Xenopus histone gene fragment X1-hi-1 represents such a unique fragment and is not present in the DNA of each single individual. The total number of genes coding for each of the nucleosomal histones is 45-50 per haploid genome.

Animals↗