24 results on '"Morvan-Dubois, G."'
Search Results
2. Differential thyroid hormone sensitivity of fast cycling progenitors in the neurogenic niches of tadpoles and juvenile frogs
- Author
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Preau, L., Le Blay, K., Saint Paul, E., Morvan-Dubois, G., Demeneix, B. A., Plasticité gliale et neuro-oncologie = Glial Plasticity (NPS-04), Neuroscience Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS), Museum National d'Histoire Naturelle (MNHN), French Agence Nationale de la Recherche ``Thrast' [11BSV2019 02], PERSU grant [SU-14-R-PERSU-04], French Ministry of Research and Education, Neurosciences Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), and Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
- Subjects
Thyroid hormone ,Endocrinology ,Xenopus ,Progenitor proliferation ,[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,Neural stem cell niche ,Cell cycle ,Adult neurogenesis ,Biochemistry ,Molecular Biology - Abstract
International audience; Adult neurogenesis occurs in neural stem cell (NSC) niches where slow cycling stem cells give rise to faster cycling progenitors. In the adult mouse NSC niche thyroid hormone, T-3, and its receptor TR alpha act as a neurogenic switch promoting progenitor cell cycle completion and neuronal differentiation. Little is known about whether and how T-3 controls proliferation of differentially cycling cells during xenopus neurogenesis. To address this question, we first used Sox3 as a marker of stem cell and progenitor populations and then applied pulse-chase EdU/IdU incorporation experiments to identify Sox3-expressing slow cycling (NSC) and fast cycling progenitor cells. We focused on the lateral ventricle of Xenopus laevis and two distinct stages of development: late embryonic development (pre-metamorphic) and juvenile frogs (post-metamorphic). These stages were selected for their relatively stable thyroid hormone availability, either side of the major dynamic phase represented by metamorphosis. TR alpha expression was found in both pre and post-metamorphic neurogenic regions. However, exogenous T-3 treatment only increased proliferation of the fast cycling Sox3+ cell population in post-metamorphic juveniles, having no detectable effect on proliferation in pre-metamorphic tadpoles. We hypothesised that the resistance of proliferative cells to exogenous T-3 in pre-metamorphic tadpoles could be related to T-3 inactivation by the inactivating Deiodinase 3 enzyme. Expression of dio3 was widespread in the tadpole neurogenic niche, but not in the juvenile neurogenic niche. Use of a T-3-reporter transgenic line showed that in juveniles, T-3 had a direct transcriptional effect on rapid cycling progenitors. Thus, the fast cycling progenitor cells in the neurogenic niche of tadpoles and juvenile frogs respond differentially to T-3 as a function of developmental stage.
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- 2016
3. Characterization of recombinant Xenopus laevis type I iodothyronine deiodinase: substitution of a proline residue in the catalytic center by serine (Pro132Ser) restores sensitivity to 6-propyl-2-thiouracil
- Author
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Kuiper Gg,, Klootwijk W,, Morvan Dubois G,, Destree O,, Darras Vm,, Van Der Geyten S,, Demeneix B,, Visser Tj.,, Evolution des régulations endocriniennes (ERE), Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), EU Crescendo, Universities of Leuven, and Rotterdam
- Abstract
In frogs such as Rana and Xenopus, metamorphosis does not occur in the absence of a functional thyroid gland. Previous studies indicated that coordinated development in frogs requires tissue and stage-dependent type II and type III iodothyronine deiodinase expression patterns to obtain requisite levels of intracellular T(3) in tissues at the appropriate stages of metamorphosis. No type I iodothyronine deiodinase (D1), defined as T(4) or reverse T(3) (rT3) outer-ring deiodinase (ORD) activity with Michaelis constant (K(m)) values in the micromolar range and sensitivity to 6-propyl-2-thiouracil (6-PTU), could be detected in tadpoles so far. We obtained a X. laevis D1 cDNA clone from brain tissue. The complete sequence of this clone (1.1 kb, including poly A tail) encodes an ORF of 252 amino acid residues with high homology to other vertebrate D1 enzymes. The core catalytic center includes a UGA-encoded selenocysteine residue, and the 3' untranslated region (about 300 nt) contains a selenocysteine insertion sequence element. Transfection of cells with an expression vector containing the full-length cDNA resulted in generation of significant deiodinase activity in the homogenates. The enzyme displayed ORD activity with T(4) (K(m) 0.5 microm) and rT3 (K(m) 0.5 microm) and inner-ring deiodinase activity with T(4) (K(m) 0.4 microm). Recombinant Xenopus D1 was essentially insensitive to inhibition by 6-PTU (IC(50) > 1 mm) but was sensitive to gold thioglucose (IC(50) 0.1 mum) and iodoacetate (IC(50) 10 microm). Because the residue 2 positions downstream from the selenocysteine is Pro in Xenopus D1 but Ser in all cloned PTU-sensitive D1 enzymes, we prepared the Pro132Ser mutant of Xenopus D1. The mutant enzyme showed strongly increased ORD activity with T(4) and rT3 (K(m) about 4 microm) and was highly sensitive to 6-PTU (IC(50) 2 microm). Little native D1 activity could be detected in Xenopus liver, kidney, brain, and gut, but significant D1 mRNA expression was observed in juvenile brain and adult liver and kidney. These results indicate the existence of a 6-PTU-insensitive D1 enzyme in X. laevis tissues, but its role during tadpole metamorphosis remains to be defined.
- Published
- 2006
4. Unliganded thyroid hormone receptor is essential for Xenopus laevis eye development
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Havis, E., Mevel S, Le, Morvan-Dubois, G., Dl, Shi, Ts, Scanlan, Ba, Demeneix, Lm, Sachs, Evolution des régulations endocriniennes (ERE), and Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS)
- Abstract
Thyroid hormone receptors generally activate transcription of target genes in the presence of thyroid hormone (T(3)) and repress their transcription in its absence. Here, we investigated the role of unliganded thyroid hormone receptor (TR) during vertebrate development using an amphibian model. Previous studies led to the hypothesis that before production of endogenous T(3), the presence of unliganded receptor is essential for premetamorphic tadpole growth. To test this hypothesis, we generated a Xenopus laevis TR beta mutant construct ineffective for gene repression owing to impaired corepressor NCoR recruitment. Overexpression by germinal transgenesis of the mutant receptor leads to lethality during early development with numerous defects in cranio-facial and eye development. These effects correlate with TR expression profiles at these early stages. Molecular analysis of transgenic mutants reveals perturbed expression of genes involved in eye development. Finally, treatment with iopanoic acid or NH-3, modulators of thyroid hormone action, leads to abnormal eye development. In conclusion, the data reveal a role of unliganded TR in eye development.
- Published
- 2006
5. Skin development in bony fish with particular emphasis on collagen deposition in the dermis of the zebrafish (Danio rerio)
- Author
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Leguellec, D., Morvan-Dubois, G., Sire, Jy, and Deleage, Gilbert
- Subjects
animal structures ,[SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology - Abstract
The first part of this article is a review of the current status of knowledge of the fish skin, with particular attention to its development. In the second part we present original results obtained in zebrafish (Danio rerio), with particular emphasis on the deposition and organisation of the dermal collagenous stroma. Using a series of zebrafish specimens aged between 15 hours postfertilization (hpf) and 4.5 years old, we have combined Transmission Electron Microscopy (TEM) observations and in situ hybridisation using type I collagen a2 chain (Col1a2) probe. Collagen fibrils, with a diameter of 22 nm, appear first in an acellular subepidermal space at 24 hpf, are first all oriented in the same direction, and form the primary dermal stroma. Subsequently, three events occur. (1) From 5-7 days pf (dpf) onwards the collagen fibrils self-organise into several lamellae arranged in a plywood-like structure, starting in the upper layers and progressing throughout the entire thickness of the dermis. (2) At 20-26 dpf, fibroblasts of unknown origin progressively invade the acellular collagenous stroma, some of them accumulating below the epidermis. (3) Concomitant with the invasion of fibroblasts, the collagen fibrils increase progressively in diameter to reach 160 nm towards the end of the fish life. In situ hybridisation experiments reveal that, between 24 and 48 hpf, the collagen matrix is produced by the epidermis only. From 72 hpf to 20-26 dpf, both the basal epidermal cells and the dermal cells bordering the deep region of the dermis are involved in the production of collagen. When the fibroblasts invade the plywood-like structure, the epidermal cells progressively cease to synthesise collagen, which from this point is produced only by the fibroblasts. This suggests that the fibroblasts secrete a still unidentified signalling molecule that downregulates collagen production by the epidermis.The first part of this article is a review of the current status of knowledge of the fish skin, with particular attention to its development. In the second part we present original results obtained in zebrafish (Danio rerio), with particular emphasis on the deposition and organisation of the dermal collagenous stroma. Using a series of zebrafish specimens aged between 15 hours postfertilization (hpf) and 4.5 years old, we have combined Transmission Electron Microscopy (TEM) observations and in situ hybridisation using type I collagen a2 chain (Col1a2) probe. Collagen fibrils, with a diameter of 22 nm, appear first in an acellular subepidermal space at 24 hpf, are first all oriented in the same direction, and form the primary dermal stroma. Subsequently, three events occur. (1) From 5-7 days pf (dpf) onwards the collagen fibrils self-organise into several lamellae arranged in a plywood-like structure, starting in the upper layers and progressing throughout the entire thickness of the dermis. (2) At 20-26 dpf, fibroblasts of unknown origin progressively invade the acellular collagenous stroma, some of them accumulating below the epidermis. (3) Concomitant with the invasion of fibroblasts, the collagen fibrils increase progressively in diameter to reach 160 nm towards the end of the fish life. In situ hybridisation experiments reveal that, between 24 and 48 hpf, the collagen matrix is produced by the epidermis only. From 72 hpf to 20-26 dpf, both the basal epidermal cells and the dermal cells bordering the deep region of the dermis are involved in the production of collagen. When the fibroblasts invade the plywood-like structure, the epidermal cells progressively cease to synthesise collagen, which from this point is produced only by the fibroblasts. This suggests that the fibroblasts secrete a still unidentified signalling molecule that downregulates collagen production by the epidermis.
- Published
- 2004
6. Capture at the single cell level of metabolic modules distinguishing aggressive and indolent glioblastoma cells.
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Saurty-Seerunghen MS, Bellenger L, El-Habr EA, Delaunay V, Garnier D, Chneiweiss H, Antoniewski C, Morvan-Dubois G, and Junier MP
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- Amino Acids metabolism, Cluster Analysis, Gene Expression Regulation, Neoplastic, Humans, Lipid Metabolism, Single-Cell Analysis, Brain Neoplasms metabolism, Glioblastoma metabolism
- Abstract
Glioblastoma cell ability to adapt their functioning to microenvironment changes is a source of the extensive intra-tumor heterogeneity characteristic of this devastating malignant brain tumor. A systemic view of the metabolic pathways underlying glioblastoma cell functioning states is lacking. We analyzed public single cell RNA-sequencing data from glioblastoma surgical resections, which offer the closest available view of tumor cell heterogeneity as encountered at the time of patients' diagnosis. Unsupervised analyses revealed that information dispersed throughout the cell transcript repertoires encoded the identity of each tumor and masked information related to cell functioning states. Data reduction based on an experimentally-defined signature of transcription factors overcame this hurdle. It allowed cell grouping according to their tumorigenic potential, regardless of their tumor of origin. The approach relevance was validated using independent datasets of glioblastoma cell and tissue transcriptomes, patient-derived cell lines and orthotopic xenografts. Overexpression of genes coding for amino acid and lipid metabolism enzymes involved in anti-oxidative, energetic and cell membrane processes characterized cells with high tumorigenic potential. Modeling of their expression network highlighted the very long chain polyunsaturated fatty acid synthesis pathway at the core of the network. Expression of its most downstream enzymatic component, ELOVL2, was associated with worsened patient survival, and required for cell tumorigenic properties in vivo. Our results demonstrate the power of signature-driven analyses of single cell transcriptomes to obtain an integrated view of metabolic pathways at play within the heterogeneous cell landscape of patient tumors.
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- 2019
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7. Expression of the inactivating deiodinase, Deiodinase 3, in the pre-metamorphic tadpole retina.
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Le Blay K, Préau L, Morvan-Dubois G, and Demeneix B
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- Animals, Metamorphosis, Biological, Opsins genetics, Retinal Cone Photoreceptor Cells metabolism, Thyroid Hormones metabolism, Xenopus laevis genetics, Xenopus laevis growth & development, Gene Expression Regulation, Enzymologic, Iodide Peroxidase genetics, Larva genetics, Larva growth & development, Retina growth & development, Retina metabolism
- Abstract
Thyroid hormone (TH) orchestrates amphibian metamorphosis. Thus, this developmental phase is often used to study TH-dependent responses in specific tissues. However, TH signaling appears early in development raising the question of the control of TH availability in specific cell types prior to metamorphosis. TH availability is under strict temporal and tissue-specific control by deiodinases. We examined the expression of the TH-inactivating enzyme, deiodinase type 3 (D3), during early retinal development. To this end we created a Xenopus laevis transgenic line expressing GFP from the Xenopus dio3 promoter region (pdio3) and followed pdio3-GFP expression in pre-metamorphic tadpoles. To validate retinal GFP expression in the transgenic line as a function of dio3 promoter activity, we used in situ hybridization to compare endogenous dio3 expression to reporter-driven GFP activity. Retinal expression of dio3 increased during pre-metamorphosis through stages NF41, 45 and 48. Both sets of results show dio3 to have cell-specific, dynamic expression in the pre-metamorphic retina. At stage NF48, dio3 expression co-localised with markers for photoreceptors, rods, Opsin-S cones and bipolar neurons. In contrast, in post-metamorphic juveniles dio3 expression was reduced and spatially confined to certain photoreceptors and amacrine cells. We compared dio3 expression at stages NF41 and NF48 with TH-dependent transcriptional responses using another transgenic reporter line: THbZIP-GFP and by analyzing the expression of T3-regulated genes in distinct TH availability contexts. At stage NF48, the majority of retinal cells expressing dio3 were negative for T3 signaling. Notably, most ganglion cells were virtually both dio3-free and T3-responsive. The results show that dio3 can reduce TH availability at the cellular scale. Further, a reduction in dio3 expression can trigger fine-tuned T3 action in cell-type specific maturation at the right time, as exemplified here in photoreceptor survival in the pre-metamorphic retina.
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- 2018
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8. Changes in chromatin state reveal ARNT2 at a node of a tumorigenic transcription factor signature driving glioblastoma cell aggressiveness.
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Bogeas A, Morvan-Dubois G, El-Habr EA, Lejeune FX, Defrance M, Narayanan A, Kuranda K, Burel-Vandenbos F, Sayd S, Delaunay V, Dubois LG, Parrinello H, Rialle S, Fabrega S, Idbaih A, Haiech J, Bièche I, Virolle T, Goodhardt M, Chneiweiss H, and Junier MP
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- Aged, Animals, Aryl Hydrocarbon Receptor Nuclear Translocator genetics, Basic Helix-Loop-Helix Transcription Factors genetics, Brain Neoplasms genetics, Brain Neoplasms pathology, Cells, Cultured, Epigenesis, Genetic, Gene Expression Regulation, Neoplastic, Gene Knockdown Techniques, Glioblastoma genetics, Glioblastoma pathology, Histone Code, Homeodomain Proteins metabolism, Humans, Mice, Nude, Middle Aged, Neoplasm Invasiveness genetics, Neoplasm Invasiveness pathology, Neoplasm Invasiveness physiopathology, Neoplasm Transplantation, Neoplastic Stem Cells metabolism, Neoplastic Stem Cells pathology, Oligodendrocyte Transcription Factor 2 metabolism, POU Domain Factors metabolism, SOX9 Transcription Factor metabolism, Aryl Hydrocarbon Receptor Nuclear Translocator metabolism, Basic Helix-Loop-Helix Transcription Factors metabolism, Brain Neoplasms metabolism, Chromatin metabolism, Glioblastoma metabolism
- Abstract
Although a growing body of evidence indicates that phenotypic plasticity exhibited by glioblastoma cells plays a central role in tumor development and post-therapy recurrence, the master drivers of their aggressiveness remain elusive. Here we mapped the changes in active (H3K4me3) and repressive (H3K27me3) histone modifications accompanying the repression of glioblastoma stem-like cells tumorigenicity. Genes with changing histone marks delineated a network of transcription factors related to cancerous behavior, stem state, and neural development, highlighting a previously unsuspected association between repression of ARNT2 and loss of cell tumorigenicity. Immunohistochemistry confirmed ARNT2 expression in cell sub-populations within proliferative zones of patients' glioblastoma. Decreased ARNT2 expression was consistently observed in non-tumorigenic glioblastoma cells, compared to tumorigenic cells. Moreover, ARNT2 expression correlated with a tumorigenic molecular signature at both the tissue level within the tumor core and at the single cell level in the patients' tumors. We found that ARNT2 knockdown decreased the expression of SOX9, POU3F2 and OLIG2, transcription factors implicated in glioblastoma cell tumorigenicity, and repressed glioblastoma stem-like cell tumorigenic properties in vivo. Our results reveal ARNT2 as a pivotal component of the glioblastoma cell tumorigenic signature, located at a node of a transcription factor network controlling glioblastoma cell aggressiveness.
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- 2018
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9. A driver role for GABA metabolism in controlling stem and proliferative cell state through GHB production in glioma.
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El-Habr EA, Dubois LG, Burel-Vandenbos F, Bogeas A, Lipecka J, Turchi L, Lejeune FX, Coehlo PL, Yamaki T, Wittmann BM, Fareh M, Mahfoudhi E, Janin M, Narayanan A, Morvan-Dubois G, Schmitt C, Verreault M, Oliver L, Sharif A, Pallud J, Devaux B, Puget S, Korkolopoulou P, Varlet P, Ottolenghi C, Plo I, Moura-Neto V, Virolle T, Chneiweiss H, and Junier MP
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- Aged, Animals, Brain metabolism, Brain pathology, Brain surgery, Brain Neoplasms pathology, Brain Neoplasms surgery, Carcinogenesis pathology, Cell Death physiology, Cell Proliferation physiology, Child, Child, Preschool, Female, Glioma pathology, Glioma surgery, Humans, Male, Mice, Nude, Middle Aged, Neoplasm Transplantation, Neoplastic Stem Cells pathology, Succinate-Semialdehyde Dehydrogenase metabolism, Brain Neoplasms metabolism, Carcinogenesis metabolism, Glioma metabolism, Hydroxybutyrates metabolism, Neoplastic Stem Cells metabolism, gamma-Aminobutyric Acid metabolism
- Abstract
Cell populations with differing proliferative, stem-like and tumorigenic states co-exist in most tumors and especially malignant gliomas. Whether metabolic variations can drive this heterogeneity by controlling dynamic changes in cell states is unknown. Metabolite profiling of human adult glioblastoma stem-like cells upon loss of their tumorigenicity revealed a switch in the catabolism of the GABA neurotransmitter toward enhanced production and secretion of its by-product GHB (4-hydroxybutyrate). This switch was driven by succinic semialdehyde dehydrogenase (SSADH) downregulation. Enhancing GHB levels via SSADH downregulation or GHB supplementation triggered cell conversion into a less aggressive phenotypic state. GHB affected adult glioblastoma cells with varying molecular profiles, along with cells from pediatric pontine gliomas. In all cell types, GHB acted by inhibiting α-ketoglutarate-dependent Ten-eleven Translocations (TET) activity, resulting in decreased levels of the 5-hydroxymethylcytosine epigenetic mark. In patients, low SSADH expression was correlated with high GHB/α-ketoglutarate ratios, and distinguished weakly proliferative/differentiated glioblastoma territories from proliferative/non-differentiated territories. Our findings support an active participation of metabolic variations in the genesis of tumor heterogeneity.
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- 2017
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10. Differential thyroid hormone sensitivity of fast cycling progenitors in the neurogenic niches of tadpoles and juvenile frogs.
- Author
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Préau L, Le Blay K, Saint Paul E, Morvan-Dubois G, and Demeneix BA
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- Animals, Brain drug effects, Brain metabolism, Cell Proliferation drug effects, Female, Gene Expression Regulation, Developmental drug effects, Larva drug effects, Larva metabolism, Male, Receptors, Thyroid Hormone metabolism, Signal Transduction drug effects, Xenopus Proteins genetics, Xenopus Proteins metabolism, Cell Cycle drug effects, Neural Stem Cells cytology, Neurogenesis drug effects, Stem Cell Niche drug effects, Thyroid Hormones pharmacology, Xenopus laevis growth & development
- Abstract
Adult neurogenesis occurs in neural stem cell (NSC) niches where slow cycling stem cells give rise to faster cycling progenitors. In the adult mouse NSC niche thyroid hormone, T3, and its receptor TRα act as a neurogenic switch promoting progenitor cell cycle completion and neuronal differentiation. Little is known about whether and how T3 controls proliferation of differentially cycling cells during xenopus neurogenesis. To address this question, we first used Sox3 as a marker of stem cell and progenitor populations and then applied pulse-chase EdU/IdU incorporation experiments to identify Sox3-expressing slow cycling (NSC) and fast cycling progenitor cells. We focused on the lateral ventricle of Xenopus laevis and two distinct stages of development: late embryonic development (pre-metamorphic) and juvenile frogs (post-metamorphic). These stages were selected for their relatively stable thyroid hormone availability, either side of the major dynamic phase represented by metamorphosis. TRα expression was found in both pre and post-metamorphic neurogenic regions. However, exogenous T3 treatment only increased proliferation of the fast cycling Sox3+ cell population in post-metamorphic juveniles, having no detectable effect on proliferation in pre-metamorphic tadpoles. We hypothesised that the resistance of proliferative cells to exogenous T3 in pre-metamorphic tadpoles could be related to T3 inactivation by the inactivating Deiodinase 3 enzyme. Expression of dio3 was widespread in the tadpole neurogenic niche, but not in the juvenile neurogenic niche. Use of a T3-reporter transgenic line showed that in juveniles, T3 had a direct transcriptional effect on rapid cycling progenitors. Thus, the fast cycling progenitor cells in the neurogenic niche of tadpoles and juvenile frogs respond differentially to T3 as a function of developmental stage., (Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.)
- Published
- 2016
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11. Thyroid hormone signaling during early neurogenesis and its significance as a vulnerable window for endocrine disruption.
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Préau L, Fini JB, Morvan-Dubois G, and Demeneix B
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- Adult, Animals, Female, Humans, Models, Animal, Nervous System drug effects, Nervous System metabolism, Pregnancy, Receptors, Thyroid Hormone antagonists & inhibitors, Receptors, Thyroid Hormone genetics, Receptors, Thyroid Hormone metabolism, Signal Transduction drug effects, Signal Transduction genetics, Thyroid Hormones pharmacology, Embryonic Development drug effects, Embryonic Development genetics, Endocrine Disruptors toxicity, Neurogenesis drug effects, Neurogenesis genetics, Thyroid Hormones physiology
- Abstract
The essential roles of thyroid hormone (TH) in perinatal brain development have been known for decades. More recently, many of the molecular mechanisms underlying the multiple effects of TH on proliferation, differentiation, migration, synaptogenesis and myelination in the developing nervous system have been elucidated. At the same time data from both epidemiological studies and animal models have revealed that the influence of thyroid signaling on development of the nervous system, extends to all periods of life, from early embryogenesis to neurogenesis in the adult brain. This review focuses on recent insights into the actions of TH during early neurogenesis. A key concept is that, in contrast to the previous ideas that only the unliganded receptor was implicated in these early phases, a critical role of the ligand, T3, is increasingly recognized. These findings are considered in the light of increasing knowledge of cell specific control of T3 availability as a function of deiodinase activity and transporter expression. These requirements for TH in the early stages of neurogenesis take on new relevance given the increasing epidemiological data on adverse effects of TH lack in early pregnancy on children's neurodevelopmental outcome. These ideas lead logically into a discussion on how the actions of TH during the first phases of neurogenesis can be potentially disrupted by gestational iodine lack and/or chemical pollution. This article is part of a Special Issue entitled: Nuclear receptors in animal development., (Copyright © 2014 Elsevier B.V. All rights reserved.)
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- 2015
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12. Nogo receptor inhibition enhances functional recovery following lysolecithin-induced demyelination in mouse optic chiasm.
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Pourabdolhossein F, Mozafari S, Morvan-Dubois G, Mirnajafi-Zadeh J, Lopez-Juarez A, Pierre-Simons J, Demeneix BA, and Javan M
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- Animals, Basic Helix-Loop-Helix Transcription Factors genetics, Basic Helix-Loop-Helix Transcription Factors metabolism, Bromodeoxyuridine administration & dosage, Cell Movement, Cell Proliferation, Demyelinating Diseases chemically induced, Demyelinating Diseases genetics, Demyelinating Diseases pathology, Evoked Potentials, Visual, GPI-Linked Proteins antagonists & inhibitors, GPI-Linked Proteins genetics, GPI-Linked Proteins metabolism, Gene Expression Regulation, Injections, Intraventricular, Lysophosphatidylcholines, Male, Mice, Mice, Inbred C57BL, Microinjections, Myelin Proteins genetics, Myelin Proteins metabolism, Myelin Sheath pathology, Nerve Tissue Proteins genetics, Nerve Tissue Proteins metabolism, Nogo Receptor 1, Oligodendrocyte Transcription Factor 2, Optic Chiasm pathology, RNA, Small Interfering genetics, RNA, Small Interfering metabolism, Receptors, Cell Surface antagonists & inhibitors, Receptors, Cell Surface metabolism, Stem Cells cytology, Stem Cells metabolism, Time Factors, Demyelinating Diseases therapy, Myelin Proteins antagonists & inhibitors, Myelin Sheath metabolism, Optic Chiasm metabolism, Receptors, Cell Surface genetics, Recovery of Function
- Abstract
Background: Inhibitory factors have been implicated in the failure of remyelination in demyelinating diseases. Myelin associated inhibitors act through a common receptor called Nogo receptor (NgR) that plays critical inhibitory roles in CNS plasticity. Here we investigated the effects of abrogating NgR inhibition in a non-immune model of focal demyelination in adult mouse optic chiasm., Methodology/principal Findings: A focal area of demyelination was induced in adult mouse optic chiasm by microinjection of lysolecithin. To knock down NgR levels, siRNAs against NgR were intracerebroventricularly administered via a permanent cannula over 14 days, Functional changes were monitored by electrophysiological recording of latency of visual evoked potentials (VEPs). Histological analysis was carried out 3, 7 and 14 days post demyelination lesion. To assess the effect of NgR inhibition on precursor cell repopulation, BrdU was administered to the animals prior to the demyelination induction. Inhibition of NgR significantly restored VEPs responses following optic chiasm demyelination. These findings were confirmed histologically by myelin specific staining. siNgR application resulted in a smaller lesion size compared to control. NgR inhibition significantly increased the numbers of BrdU+/Olig2+ progenitor cells in the lesioned area and in the neurogenic zone of the third ventricle. These progenitor cells (Olig2+ or GFAP+) migrated away from this area as a function of time., Conclusions/significance: Our results show that inhibition of NgR facilitate myelin repair in the demyelinated chiasm, with enhanced recruitment of proliferating cells to the lesion site. Thus, antagonizing NgR function could have therapeutic potential for demyelinating disorders such as Multiple Sclerosis.
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- 2014
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13. Thyroid hormone signaling and adult neurogenesis in mammals.
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Remaud S, Gothié JD, Morvan-Dubois G, and Demeneix BA
- Abstract
The vital roles of thyroid hormone in multiple aspects of perinatal brain development have been known for over a century. In the last decades, the molecular mechanisms underlying effects of thyroid hormone on proliferation, differentiation, migration, synaptogenesis, and myelination in the developing nervous system have been gradually dissected. However, recent data reveal that thyroid signaling influences neuronal development throughout life, from early embryogenesis to the neurogenesis in the adult brain. This review deals with the latter phase and analyses current knowledge on the role of T3, the active form of thyroid hormone, and its receptors in regulating neural stem cell function in the hippocampus and the subventricular zone, the two principal sites harboring neurogenesis in the adult mammalian brain. In particular, we discuss the critical roles of T3 and TRα1 in commitment to a neuronal phenotype, a process that entails the repression of a number of genes notably that encoding the pluripotency factor, Sox2. Furthermore, the question of the relevance of thyroid hormone control of adult neurogenesis is considered in the context of brain aging, cognitive decline, and neurodegenerative disease.
- Published
- 2014
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14. Inhibition of Sox2 Expression in the Adult Neural Stem Cell Niche In Vivo by Monocationic-based siRNA Delivery.
- Author
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Remaud S, López-Juárez SA, Bolcato-Bellemin AL, Neuberg P, Stock F, Bonnet ME, Ghaddab R, Clerget-Froidevaux MS, Pierre-Simons J, Erbacher P, Demeneix BA, and Morvan-Dubois G
- Abstract
RNA interference (RNAi) is a major tool for basic and applied investigations. However, obtaining RNAi data that have physiological significance requires investigation of regulations and therapeutic strategies in appropriate in vivo settings. To examine in vivo gene regulation and protein function in the adult neural stem cell (NSC) niche, we optimized a new non-viral vector for delivery of siRNA into the subventricular zone (SVZ). This brain region contains the neural stem and progenitor cells populations that express the stem cell marker, SOX2. Temporally and spatially controlled Sox2 knockdown was achieved using the monocationic lipid vector, IC10. siRNA/IC10 complexes were stable over time and smaller (<40 nm) than jetSi complexes (≈400 nm). Immunocytochemistry showed that siRNA/IC10 complexes efficiently target both the progenitor and stem cell populations in the adult SVZ. Injection of the complexes into the lateral brain ventricle resulted in specific knockdown of Sox2 in the SVZ. Furthermore, IC10-mediated transient in vivo knockdown of Sox2-modulated expression of several genes implicated in NSC maintenance. Taken together, these data show that IC10 cationic lipid formulation can efficiently vectorize siRNA in a specific area of the adult mouse brain, achieving spatially and temporally defined loss of function.Molecular Therapy-Nucleic Acids (2013) 2, e89; doi:10.1038/mtna.2013.8; published online 23 April 2013.
- Published
- 2013
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15. Is thyroid hormone signaling relevant for vertebrate embryogenesis?
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Morvan-Dubois G, Fini JB, and Demeneix BA
- Subjects
- Animals, Endocrine System metabolism, Humans, Receptors, Thyroid Hormone metabolism, Embryonic Development, Signal Transduction, Thyroid Hormones metabolism, Vertebrates embryology, Vertebrates metabolism
- Abstract
Classically, thyroid hormones (THs) have been primarily associated with postembryonic development (Tata, 1968), notably metamorphosis in anuran amphibians and flat fish. This period is parallel to the perinatal period in man and many marked developmental transitions in other species. As amply described in other chapters, metamorphosis is characterized by a peak of thyroxine (T(4)) and triiodothyronine (T(3)) that is synchronous with the metamorphic climax. In contrast, the developmental period that characterizes embryonic development prior to the significant production of TH by the endogenous thyroid gland has received little attention. Furthermore, the prevailing concepts of TH physiology during this period have been framed by two observations in amphibians and mammals: first, TRs are expressed, while circulating TH levels are much lower than those during metamorphosis and, second, extrapolating from the knowledge largely obtained from in vitro models, in the absence of TH, the aporeceptor represses target gene transcription during premetamorphic development. We propose to revisit both concepts in the light of accumulating data, first, on TH availability both in eggs and in embryos and, second, on the increasing knowledge of the complexity of TR and TH control of transcription., (Copyright © 2013 Elsevier Inc. All rights reserved.)
- Published
- 2013
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16. [Thyroid hormone signalling favors neural stem cell commitment].
- Author
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Remaud S, Morvan-Dubois G, and Demeneix BA
- Subjects
- Adult Stem Cells drug effects, Adult Stem Cells metabolism, Animals, Cell Differentiation physiology, Gene Expression Regulation, Developmental drug effects, Humans, Mice, Models, Biological, Neural Stem Cells drug effects, Neurogenesis physiology, SOXB1 Transcription Factors genetics, SOXB1 Transcription Factors metabolism, Signal Transduction drug effects, Thyroid Hormone Receptors alpha metabolism, Thyroid Hormone Receptors alpha physiology, Thyroid Hormones metabolism, Thyroid Hormones pharmacology, Adult Stem Cells physiology, Neural Stem Cells physiology, Thyroid Hormones physiology
- Published
- 2012
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17. Thyroid hormone signaling acts as a neurogenic switch by repressing Sox2 in the adult neural stem cell niche.
- Author
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López-Juárez A, Remaud S, Hassani Z, Jolivet P, Pierre Simons J, Sontag T, Yoshikawa K, Price J, Morvan-Dubois G, and Demeneix BA
- Subjects
- Animals, Cell Movement genetics, Doublecortin Protein, Enzyme Repression genetics, Mice, Mice, Mutant Strains, RNA, Small Interfering genetics, SOXB1 Transcription Factors genetics, Signal Transduction, Stem Cell Niche genetics, Thyroid Hormone Receptors alpha genetics, Thyroid Hormones genetics, Transgenes genetics, Adult Stem Cells physiology, Neural Stem Cells physiology, Neurogenesis genetics, SOXB1 Transcription Factors metabolism, Thyroid Hormone Receptors alpha metabolism, Thyroid Hormones metabolism
- Abstract
The subventricular zone (SVZ) neural stem cell niche contains mixed populations of stem cells, transit-amplifying cells, and migrating neuroblasts. Deciphering how endogenous signals, such as hormones, affect the balance between these cell types is essential for understanding the physiology of niche plasticity and homeostasis. We show that Thyroid Hormone (T(3)) and its receptor, TRα1, are directly involved in maintaining this balance. TRα1 is expressed in amplifying and migrating cells. In vivo gain- and loss-of-function experiments demonstrate first, that T(3)/TRα1 directly repress Sox2 expression, and second, that TRα1 overexpression in the niche favors the appearance of DCX+ migrating neuroblasts. Lack of TRα increases numbers of SOX2+ cells in the SVZ. Hypothyroidism increases proportions of cells in interphase. Thus, in the adult SVZ, T(3)/TRα1 together favor neural stem cell commitment and progression toward a migrating neuroblast phenotype; this transition correlates with T(3)/TRα1-dependent transcriptional repression of Sox2., (Copyright © 2012 Elsevier Inc. All rights reserved.)
- Published
- 2012
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18. Xenopus laevis as a model for studying thyroid hormone signalling: from development to metamorphosis.
- Author
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Morvan-Dubois G, Demeneix BA, and Sachs LM
- Subjects
- Animals, Embryo, Nonmammalian metabolism, Embryonic Development, Enzyme Activation, Gene Expression Regulation, Developmental, Iodide Peroxidase chemistry, Iodide Peroxidase genetics, Iodide Peroxidase metabolism, Larva genetics, Larva growth & development, Larva metabolism, Ligands, Models, Animal, Receptors, Thyroid Hormone physiology, Xenopus Proteins chemistry, Xenopus Proteins genetics, Xenopus Proteins metabolism, Xenopus laevis, Signal Transduction, Thyroid Hormones metabolism
- Abstract
Amphibian metamorphosis is a well-established model for dissecting the mechanisms underlying thyroid hormone (TH) action. How the pro-hormone, T(4), the active form, T(3), the deiodinases and the nuclear receptors (TRs) contribute to metamorphosis in Xenopus has been extensively investigated. Our recent work has concentrated on two key ideas in TH signalling in Xenopus: first, that there could be active roles for both liganded and unliganded receptors, and second, that ligand availability is a determining factor orchestrating these actions and is tightly controlled in target tissues. Recently, we addressed these questions at stages preceding metamorphosis, i.e. during embryogenesis, before differentiation of a functional thyroid gland. We show that repression by unliganded TR is essential to craniofacial and eye development during early development and that at these stages all three deiodinases are active. These results open new perspectives on the potential roles of TH signalling during embryogenesis.
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- 2008
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19. Unliganded thyroid hormone receptor is essential for Xenopus laevis eye development.
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Havis E, Le Mevel S, Morvan Dubois G, Shi DL, Scanlan TS, Demeneix BA, and Sachs LM
- Subjects
- Animals, Contrast Media pharmacology, Iopanoic Acid pharmacology, Ligands, Nuclear Proteins genetics, Nuclear Proteins metabolism, Receptors, Thyroid Hormone genetics, Xenopus Proteins genetics, Xenopus laevis, Eye embryology, Gene Expression Regulation, Developmental drug effects, Gene Expression Regulation, Developmental genetics, Mutation, Receptors, Thyroid Hormone metabolism, Xenopus Proteins metabolism
- Abstract
Thyroid hormone receptors generally activate transcription of target genes in the presence of thyroid hormone (T(3)) and repress their transcription in its absence. Here, we investigated the role of unliganded thyroid hormone receptor (TR) during vertebrate development using an amphibian model. Previous studies led to the hypothesis that before production of endogenous T(3), the presence of unliganded receptor is essential for premetamorphic tadpole growth. To test this hypothesis, we generated a Xenopus laevis TR beta mutant construct ineffective for gene repression owing to impaired corepressor NCoR recruitment. Overexpression by germinal transgenesis of the mutant receptor leads to lethality during early development with numerous defects in cranio-facial and eye development. These effects correlate with TR expression profiles at these early stages. Molecular analysis of transgenic mutants reveals perturbed expression of genes involved in eye development. Finally, treatment with iopanoic acid or NH-3, modulators of thyroid hormone action, leads to abnormal eye development. In conclusion, the data reveal a role of unliganded TR in eye development.
- Published
- 2006
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20. Deiodinase activity is present in Xenopus laevis during early embryogenesis.
- Author
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Morvan Dubois G, Sebillot A, Kuiper GG, Verhoelst CH, Darras VM, Visser TJ, and Demeneix BA
- Subjects
- Animals, Embryonic Development, Female, Gene Expression Regulation, Developmental, Gene Expression Regulation, Enzymologic, In Situ Hybridization, Isoenzymes metabolism, Metamorphosis, Biological, Ovum metabolism, Ovum physiology, RNA analysis, RNA biosynthesis, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction physiology, Thyroid Hormones metabolism, Thyroid Hormones physiology, Thyroxine metabolism, Thyroxine physiology, Triiodothyronine metabolism, Xenopus laevis, Embryo, Nonmammalian enzymology, Iodide Peroxidase metabolism
- Abstract
Thyroid hormones orchestrate amphibian metamorphosis. The type 2 and type 3 deiodinases make vital contributions to this process by controlling levels of the thyroid hormones T(4) and T(3) available to different tissues. Because the tadpole thyroid gland is not functional until stage NF44, it has been widely assumed that thyroid signaling is absent during amphibian early development, thyroid hormone only becoming a major regulator during premetamorphic stages. Similarly, in mammals, thyroid function is known to be essential to neuronal development, especially during the perinatal stages, but again little is known about early stages of development. Here we demonstrate that key elements of thyroid hormone signaling are present during early development of Xenopus. In particular, we find functional thyroid hormone-activating deiodinases and significant levels of their substrates, T(4) and T(3), during early embryogenesis. Furthermore, we have further characterized a recently identified deiodinase in amphibians, homologous to mammalian type 1 deiodinase (D1). This enzyme is expressed in marked, spatially defined patterns during embryogenesis. The patterns of expression of type 1 deiodinase are distinct from those of type 2 and type 3 deiodinases. Deiodinase expression is found in neurogenic areas from stage NF30 onward, both in the central and peripheral nervous systems. We conclude that both activating and inactivating deiodinases show dynamic patterns of expression during early embryogenesis in amphibians, particularly in neurogenic areas. These findings suggest that thyroid hormone signaling is a key component of early neuronal development in vertebrates.
- Published
- 2006
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21. Characterization of recombinant Xenopus laevis type I iodothyronine deiodinase: substitution of a proline residue in the catalytic center by serine (Pro132Ser) restores sensitivity to 6-propyl-2-thiouracil.
- Author
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Kuiper GG, Klootwijk W, Morvan Dubois G, Destree O, Darras VM, Van der Geyten S, Demeneix B, and Visser TJ
- Subjects
- 3' Untranslated Regions, Amino Acid Sequence, Animals, Base Sequence, Catalytic Domain, Kinetics, Molecular Sequence Data, Propylthiouracil pharmacology, Rats, Selenocysteine chemistry, Sequence Homology, Amino Acid, Xenopus laevis, Iodide Peroxidase chemistry, Iodide Peroxidase genetics, Mutation, Proline chemistry, Serine chemistry
- Abstract
In frogs such as Rana and Xenopus, metamorphosis does not occur in the absence of a functional thyroid gland. Previous studies indicated that coordinated development in frogs requires tissue and stage-dependent type II and type III iodothyronine deiodinase expression patterns to obtain requisite levels of intracellular T(3) in tissues at the appropriate stages of metamorphosis. No type I iodothyronine deiodinase (D1), defined as T(4) or reverse T(3) (rT3) outer-ring deiodinase (ORD) activity with Michaelis constant (K(m)) values in the micromolar range and sensitivity to 6-propyl-2-thiouracil (6-PTU), could be detected in tadpoles so far. We obtained a X. laevis D1 cDNA clone from brain tissue. The complete sequence of this clone (1.1 kb, including poly A tail) encodes an ORF of 252 amino acid residues with high homology to other vertebrate D1 enzymes. The core catalytic center includes a UGA-encoded selenocysteine residue, and the 3' untranslated region (about 300 nt) contains a selenocysteine insertion sequence element. Transfection of cells with an expression vector containing the full-length cDNA resulted in generation of significant deiodinase activity in the homogenates. The enzyme displayed ORD activity with T(4) (K(m) 0.5 microm) and rT3 (K(m) 0.5 microm) and inner-ring deiodinase activity with T(4) (K(m) 0.4 microm). Recombinant Xenopus D1 was essentially insensitive to inhibition by 6-PTU (IC(50) > 1 mm) but was sensitive to gold thioglucose (IC(50) 0.1 mum) and iodoacetate (IC(50) 10 microm). Because the residue 2 positions downstream from the selenocysteine is Pro in Xenopus D1 but Ser in all cloned PTU-sensitive D1 enzymes, we prepared the Pro132Ser mutant of Xenopus D1. The mutant enzyme showed strongly increased ORD activity with T(4) and rT3 (K(m) about 4 microm) and was highly sensitive to 6-PTU (IC(50) 2 microm). Little native D1 activity could be detected in Xenopus liver, kidney, brain, and gut, but significant D1 mRNA expression was observed in juvenile brain and adult liver and kidney. These results indicate the existence of a 6-PTU-insensitive D1 enzyme in X. laevis tissues, but its role during tadpole metamorphosis remains to be defined.
- Published
- 2006
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22. Skin development in bony fish with particular emphasis on collagen deposition in the dermis of the zebrafish (Danio rerio).
- Author
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Le Guellec D, Morvan-Dubois G, and Sire JY
- Subjects
- Animals, Cell Movement, Collagen biosynthesis, Collagen ultrastructure, Collagen Type I ultrastructure, Dermis chemistry, Dermis ultrastructure, Down-Regulation, Embryo, Nonmammalian metabolism, Embryo, Nonmammalian ultrastructure, Epidermis metabolism, Epidermis ultrastructure, Extracellular Matrix metabolism, Extracellular Matrix ultrastructure, Fibroblasts metabolism, Fibroblasts physiology, Fibroblasts ultrastructure, Gene Expression Regulation, Developmental, In Situ Hybridization, Larva, Models, Biological, RNA, Messenger metabolism, RNA, Messenger ultrastructure, Skin embryology, Skin ultrastructure, Time Factors, Collagen Type I metabolism, Dermis metabolism, Skin metabolism, Zebrafish growth & development
- Abstract
The first part of this article is a review of the current status of knowledge of the fish skin, with particular attention to its development. In the second part we present original results obtained in zebrafish (Danio rerio), with particular emphasis on the deposition and organisation of the dermal collagenous stroma. Using a series of zebrafish specimens aged between 15 hours postfertilization (hpf) and 4.5 years old, we have combined Transmission Electron Microscopy (TEM) observations and in situ hybridisation using type I collagen a2 chain (Col1a2) probe. Collagen fibrils, with a diameter of 22 nm, appear first in an acellular subepidermal space at 24 hpf, are first all oriented in the same direction, and form the primary dermal stroma. Subsequently, three events occur. (1) From 5-7 days pf (dpf) onwards the collagen fibrils self-organise into several lamellae arranged in a plywood-like structure, starting in the upper layers and progressing throughout the entire thickness of the dermis. (2) At 20-26 dpf, fibroblasts of unknown origin progressively invade the acellular collagenous stroma, some of them accumulating below the epidermis. (3) Concomitant with the invasion of fibroblasts, the collagen fibrils increase progressively in diameter to reach 160 nm towards the end of the fish life. In situ hybridisation experiments reveal that, between 24 and 48 hpf, the collagen matrix is produced by the epidermis only. From 72 hpf to 20-26 dpf, both the basal epidermal cells and the dermal cells bordering the deep region of the dermis are involved in the production of collagen. When the fibroblasts invade the plywood-like structure, the epidermal cells progressively cease to synthesise collagen, which from this point is produced only by the fibroblasts. This suggests that the fibroblasts secrete a still unidentified signalling molecule that downregulates collagen production by the epidermis.
- Published
- 2004
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23. Phylogenetic analysis of vertebrate fibrillar collagen locates the position of zebrafish alpha3(I) and suggests an evolutionary link between collagen alpha chains and hox clusters.
- Author
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Morvan-Dubois G, Le Guellec D, Garrone R, Zylberberg L, and Bonnaud L
- Subjects
- Amino Acid Sequence, Animals, Genes, Homeobox, Molecular Sequence Data, Multigene Family, Phylogeny, Sequence Alignment, Collagen Type I genetics, Evolution, Molecular, Zebrafish genetics
- Abstract
Type I collagen in tetrapods is usually a heterotrimeric molecule composed of two alpha1 and one alpha2 chains. In some teleosts, a third alpha chain has been identified by chromatography, suggesting that type I collagen should also exist as an alpha1(I)alpha2(I)alpha3(I) heterotrimer. We prepared, from zebrafish, three distinct cDNAs identified to be those of the collagen alpha1(I), alpha2(I), and alpha3(I) chains. In this study on the evolution of fibrillar collagen alpha chains and their relationships, an exhaustive phylogenetic analysis, using vertebrate fibrillar collagen sequences, showed that each alpha chain constitutes a monophyletic cluster. Results obtained with the newly isolated sequences of the zebrafish showed that the alpha3(I) chain is phylogenetically close to the alpha1(I) chain and support the hypothesis that the alpha3(I) chain arose from a duplication of the alpha1(I) gene. The duplication might occur during the duplication of the actinopterygian genome, soon after the divergence of actinopterygians and sarcopterygians, a hypothesis supported by the demonstration of a syntenic evolution between a set of fibrillar collagen genes and Hox clusters in mammals. An evolutionary scenario is proposed in which phylogenetic relationships of the alpha chains of fibrillar collagens of vertebrates could be related to Hox cluster history.
- Published
- 2003
- Full Text
- View/download PDF
24. Sequence and embryonic expression of collagen XVIII NC1 domain (endostatin) in the zebrafish.
- Author
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Haftek Z, Morvan-Dubois G, Thisse B, Thisse C, Garrone R, and Le Guellec D
- Subjects
- Amino Acid Sequence, Animals, Base Sequence, Endostatins biosynthesis, In Situ Hybridization, Molecular Sequence Data, Zebrafish metabolism, Endostatins genetics, Zebrafish embryology
- Abstract
Endostatin, located in the NC1 domain of the collagen XVIII, is believed to inhibit the migration and proliferation of endothelial cells (Fed. Am. Soc. Exp. Biol. J. 15 (2001) 1044) and to play a role in axon guidance in Caenorhabditis elegans (J. Cell Biol. 152 (2001) 1219). Zebrafish is an attractive vertebrate model to determine the role of endostatin and the entire molecule of collagen XVIII during vertebrate development. Therefore, we have investigated the expression pattern of COL18A1 in zebrafish embryos from the segmentation to the hatching period stages.
- Published
- 2003
- Full Text
- View/download PDF
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