32 results on '"Knibiehler, B."'
Search Results
2. Studies on chromatin organization in a nucleolus without fibrillar centres: Presence of a sub-nucleolar structure in KCo cells of Drosophila
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Knibiehler, B., Mirre, C., Navarro, A., and Rosset, R.
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- 1984
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3. Quantitative ultrastructural analysis of fibrillar centers in the mouse: Correlation of their number and volume with nucleolar organizers-activity
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Mirre, C. and Knibiehler, B.
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- 1984
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4. Apelin signalling: a promising pathway from cloning to pharmacology
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Masri, B., Knibiehler, B., and Audigier, Y.
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CARDIOVASCULAR system , *MICROBIAL genetics , *CENTRAL nervous system , *LENTIVIRUS diseases - Abstract
Abstract: The discovery of new signalling pathways is always followed by the development of pharmacological agents as drugs that can be used in the treatment of diseases resulting from a dysfunction of the signalling pathway in question. Apelin signalling plays a role in the central and peripheral regulation of the cardiovascular system, in water and food intake, and possibly in immune function. Up-regulation of ligand and receptor is also associated with pathophysiological states such as cardiac dysfunction and neovascularisation. Finally, the apelin receptor is a coreceptor for the entry of several HIV-1 and SIV strains. In view of these features, the apelin receptor constitutes a very interesting target for the design of new drugs for treating the prime causes of human mortality. [Copyright &y& Elsevier]
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- 2005
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5. Collagen IV is present in the developing CNS during Drosophila neurogenesis.
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Mirre, C., Le Parco, Y., and Knibiehler, B.
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- 1992
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6. Sex vesicle-associated nucleolar organizers in mouse spermatocytes: localization, structure, and function.
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Knibiehler, B., Mirre, C., Hartung, M., Jean, P., Stahl, A., de Lanversin, A., and Soler, M.
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- 1981
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7. Protamine is an antagonist of Apelin receptor, and its activity is reversed by heparin
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Barak, L.S., Le Gonidec, S., Wanecq, E., Roth, B.L., Masri, B., Audigier, Y., Huang, X.-P., Knibiehler, B., Bai, Y., Chaves-Almagro, C., Prats, H., Smith, A., Caron, M.G., Kang, H.J., and Valet, P.
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3. Good health - Abstract
In the accompanying Comment, Suzuki et al. confirmed our previous findings that the ketamine metabolite (2R,6R)-hydroxynorketamine (HNK) does not functionally inhibit the NMDAR at concentrations relevant to its antidepressant actions recently reported in mice (that is, approximately 10 μM).
8. Identification and pharmacological properties of an antagonist of apelin receptors
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Masri, B., Barak, L.S., Bai, Y., Knibiehler, B., Caron, M.G., and Audigier, Y.
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- 2010
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9. Upregulated Apelin Signaling in Pancreatic Cancer Activates Oncogenic Signaling Pathways to Promote Tumor Development.
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Chaves-Almagro C, Auriau J, Dortignac A, Clerc P, Lulka H, Deleruyelle S, Projetti F, Nakhlé J, Frances A, Berta J, Gigoux V, Fourmy D, Dufresne M, Gomez-Brouchet A, Guillermet-Guibert J, Cordelier P, Knibiehler B, Jockers R, Valet P, Audigier Y, and Masri B
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- Animals, Cyclin D1 metabolism, Glucose, Humans, Mice, Oncogenes, Phosphatidylinositol 3-Kinases metabolism, Proto-Oncogene Proteins c-akt metabolism, Receptors, G-Protein-Coupled genetics, Receptors, G-Protein-Coupled metabolism, Signal Transduction, beta Catenin metabolism, Pancreatic Neoplasms, Adenocarcinoma pathology, Apelin metabolism, Apelin Receptors metabolism, Carcinoma, Pancreatic Ductal genetics, Pancreatic Neoplasms pathology
- Abstract
Despite decades of effort in understanding pancreatic ductal adenocarcinoma (PDAC), there is still a lack of innovative targeted therapies for this devastating disease. Herein, we report the expression of apelin and its receptor, APJ, in human pancreatic adenocarcinoma and its protumoral function. Apelin and APJ protein expression in tumor tissues from patients with PDAC and their spatiotemporal pattern of expression in engineered mouse models of PDAC were investigated by immunohistochemistry. Apelin signaling function in tumor cells was characterized in pancreatic tumor cell lines by Western blot as well as proliferation, migration assays and in murine orthotopic xenograft experiments. In premalignant lesions, apelin was expressed in epithelial lesions whereas APJ was found in isolated cells tightly attached to premalignant lesions. However, in the invasive stage, apelin and APJ were co-expressed by tumor cells. In human tumor cells, apelin induced a long-lasting activation of PI3K/Akt, upregulated β-catenin and the oncogenes c-myc and cyclin D1 and promoted proliferation, migration and glucose uptake. Apelin receptor blockades reduced cancer cell proliferation along with a reduction in pancreatic tumor burden. These findings identify the apelin signaling pathway as a new actor for PDAC development and a novel therapeutic target for this incurable disease.
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- 2022
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10. Protamine is an antagonist of apelin receptor, and its activity is reversed by heparin.
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Le Gonidec S, Chaves-Almagro C, Bai Y, Kang HJ, Smith A, Wanecq E, Huang XP, Prats H, Knibiehler B, Roth BL, Barak LS, Caron MG, Valet P, Audigier Y, and Masri B
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- Animals, Apelin Receptors, Cell Line, Tumor, Female, Gene Expression Regulation drug effects, Gene Expression Regulation physiology, HEK293 Cells, Humans, Male, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Receptors, G-Protein-Coupled genetics, Receptors, G-Protein-Coupled metabolism, Heparin pharmacology, Protamines pharmacology, Receptors, G-Protein-Coupled antagonists & inhibitors
- Abstract
Apelin signaling plays an important role during embryo development and regulates angiogenesis, cardiovascular activity, and energy metabolism in adulthood. Overexpression and hyperactivity of this signaling pathway is observed in various pathologic states, such as cardiovascular diseases and cancer, which highlights the importance of inhibiting apelin receptor (APJ); therefore, we developed a cell-based screening assay that uses fluorescence microscopy to identify APJ antagonists. This approach led us to identify the U.S. Food and Drug Administration-approved compound protamine-already used clinically after cardiac surgery-as an agent to bind to heparin and thereby reverse its anticlotting activity. Protamine displays a 390-nM affinity for APJ and behaves as a full antagonist with regard to G protein and β-arrestin-dependent intracellular signaling. Ex vivo and in vivo , protamine abolishes well-known apelin effects, such as angiogenesis, glucose tolerance, and vasodilatation. Remarkably, protamine antagonist activity is fully reversed by heparin treatment both in vitro and in vivo Thus, our results demonstrate a new pharmacologic property of protamine-blockade of APJ-that could explain some adverse effects observed in protamine-treated patients. Moreover, our data reveal that the established antiangiogenic activity of protamine would rely on APJ antagonism.-Le Gonidec, S., Chaves-Almagro, C., Bai, Y., Kang, H. J., Smith, A., Wanecq, E., Huang, X.-P., Prats, H., Knibiehler, B., Roth, B. L., Barak, L. S., Caron, M. G., Valet, P., Audigier, Y., Masri, B. Protamine is an antagonist of apelin receptor, and its activity is reversed by heparin., (© FASEB.)
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- 2017
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11. Therapeutic potential of interfering with apelin signalling.
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Sorli SC, van den Berghe L, Masri B, Knibiehler B, and Audigier Y
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- Apelin Receptors, Drug Design, Endothelium, Vascular drug effects, Endothelium, Vascular physiopathology, Humans, Neovascularization, Pathologic physiopathology, Neovascularization, Pathologic prevention & control, Receptors, G-Protein-Coupled antagonists & inhibitors, Signal Transduction drug effects, Receptors, G-Protein-Coupled physiology, Signal Transduction physiology
- Abstract
The apelin receptor is a G protein-coupled receptor activated by several apelin fragments. Its tissue distribution suggests that apelin signalling is involved in a broad range of physiological functions. Endothelial cells, which express high levels of apelin receptors, respond to apelin through the phosphorylation of key intracellular effectors associated with cell proliferation and migration. In addition, apelin is a mitogen for endothelial cells and exhibits angiogenic properties in matrigel experiments. This review focuses on the therapeutic potential of apelin signalling, which is associated with pathologies that result from decreased vascularisation (ischemias) or neovascularisation (retinopathies and solid tumors).
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- 2006
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12. The apelin receptor is coupled to Gi1 or Gi2 protein and is differentially desensitized by apelin fragments.
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Masri B, Morin N, Pedebernade L, Knibiehler B, and Audigier Y
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- Adipokines, Animals, Apelin, Apelin Receptors, CHO Cells, Carrier Proteins chemistry, Cricetinae, Cricetulus, GTP-Binding Protein alpha Subunits metabolism, Intercellular Signaling Peptides and Proteins, Ligands, Mice, Peptide Fragments metabolism, Carrier Proteins metabolism, Receptors, G-Protein-Coupled metabolism, Signal Transduction
- Abstract
The apelin receptor is a G protein-coupled receptor to which two ligand fragments, apelin-(65-77) and apelin-(42-77), can bind. To address the physiological significance of the existence of dual ligands for a single receptor, we first compared the ability of the apelin fragments to regulate intracellular effectors, to promote G protein coupling, and to desensitize the response in Chinese hamster ovary cells expressing the murine apelin receptor. We found that both apelin fragments inhibited adenylyl cyclase and increased the phosphorylation of ERK or Akt. Using stably transfected cells expressing a pertussis toxin-insensitive alpha(i) subunit, we demonstrated that each apelin fragment promoted coupling of the apelin receptor to either Galpha(i1) or Galpha(i2) but not to Galpha(i3). Although preincubation with each apelin fragment induced a desensitization at the level of the three effectors, preincubation with apelin-(42-77) also increased basal effector activity. In addition, a C-terminal deletion of the apelin receptor decreased the desensitization induced by apelin-(65-77) but did not alter the desensitization pattern induced by apelin-(42-77). Finally, in umbilical endothelial cells, which we have recently shown to express the apelin receptor, the Galpha(i1) and Galpha(i2) subunits are also expressed, ERK and Akt phosphorylation is desensitized after preincubation with apelin-(65-77), and basal levels of Akt phosphorylation are increased after preincubation with apelin-(42-77). In summary, apelin fragments regulate the same effectors, via the preferential coupling of the apelin receptor to G(i1) or G(i2), but they promote a differential desensitization pattern that may be central to their respective physiological roles.
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- 2006
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13. Apelin, a newly identified adipokine up-regulated by insulin and obesity.
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Boucher J, Masri B, Daviaud D, Gesta S, Guigné C, Mazzucotelli A, Castan-Laurell I, Tack I, Knibiehler B, Carpéné C, Audigier Y, Saulnier-Blache JS, and Valet P
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- Adipocytes cytology, Adipocytes metabolism, Adipokines, Adipose Tissue metabolism, Animals, Apelin, Carrier Proteins physiology, Cell Differentiation, Female, Gene Expression Regulation, Humans, Hyperinsulinism metabolism, Insulin blood, Intercellular Signaling Peptides and Proteins, Mice, Mice, Inbred C57BL, Up-Regulation, Carrier Proteins genetics, Insulin pharmacology, Obesity metabolism
- Abstract
The results presented herein demonstrate that apelin is expressed and secreted by both human and mouse adipocytes. Apelin mRNA levels in isolated adipocytes are close to other cell types present in white adipose tissue or other organs known to express apelin such as kidney, heart, and to a lesser extent brown adipose tissue. Apelin expression is increased during adipocyte differentiation stage. A comparison of four different models of obesity in mice showed a large increase in both apelin expression in fat cells and apelin plasma levels in all the hyperinsulinemia-associated obesities and clearly demonstrated that obesity or high-fat feeding are not the main determinants of the rise of apelin expression. The lack of insulin in streptozotocin-treated mice is associated with a decreased expression of apelin in adipocytes. Furthermore, apelin expression in fat cells is strongly inhibited by fasting and recovered after refeeding, in a similar way to insulin. A direct regulation of apelin expression by insulin is observed in both human and mouse adipocytes and clearly associated with the stimulation of phosphatidylinositol 3-kinase, protein kinase C, and MAPK. These data provide evidence that insulin exerts a direct control on apelin gene expression in adipocytes. In obese patients, both plasma apelin and insulin levels were significantly higher, suggesting that the regulation of apelin by insulin could influence blood concentrations of apelin. The present work identifies apelin as a novel adipocyte endocrine secretion and focuses on its potential link with obesity-associated variations of insulin sensitivity status.
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- 2005
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14. Apelin (65-77) activates p70 S6 kinase and is mitogenic for umbilical endothelial cells.
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Masri B, Morin N, Cornu M, Knibiehler B, and Audigier Y
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- Animals, CHO Cells, Cricetinae, Cricetulus, Endothelial Cells drug effects, Endothelial Cells enzymology, Enzyme Activation, Extracellular Signal-Regulated MAP Kinases antagonists & inhibitors, Flavonoids pharmacology, Humans, Pertussis Toxin pharmacology, Phosphatidylinositol 3-Kinases metabolism, Phosphorylation, Protein Kinase C physiology, Protein Kinase Inhibitors pharmacology, Protein Serine-Threonine Kinases metabolism, Proto-Oncogene Proteins metabolism, Proto-Oncogene Proteins c-akt, Signal Transduction, Sirolimus pharmacology, Umbilical Cord cytology, src-Family Kinases metabolism, Carrier Proteins pharmacology, Endothelium, Vascular enzymology, Mitogens pharmacology, Ribosomal Protein S6 Kinases, 70-kDa metabolism
- Abstract
We report here that apelin (65-77) activates p70 S6 kinase (p70S6K), not only in CHO cells that have been stably transfected with the apelin receptor, but also in umbilical endothelial cells (HUVEC), which express it endogenously. Apelin (65-77) induces a time-dependent phosphorylation of p70S6K at residues T421/S424 and T389. This dual phosphorylation is associated with two transduction cascades, involving a PI3K pathway and an ERK pathway, respectively. The PI3K pathway, which can be blocked by wortmannin, leads to phosphorylation of Akt at residues T308 or S473, which then promotes the phosphorylation of p70S6K at T421/S424 and T389. The ERK pathway is blocked by PD 098059, a MEK inhibitor, and results in the phosphorylation of p70S6K at T421/S424. Phosphorylation both of Akt and p70S6K is abrogated by pretreatment with pertussis toxin (PTX) and an inhibitor of atypical PKCs. In addition, we demonstrate that apelin (65-77) also increases the enzymatic activity of p70S6K and that the effects of the previously mentioned inhibitors on the level of T389 phosphorylation correlate with their action on enzyme activity. Interestingly, the main findings were reproduced in umbilical endothelial cells and apelin (65-77) promoted thymidine incorporation into DNA of these cells, revealing that apelin is a new mitogenic peptide for the endothelial cell.
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- 2004
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15. The msr/apj gene encoding the apelin receptor is an early and specific marker of the venous phenotype in the retinal vasculature.
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Saint-Geniez M, Argence CB, Knibiehler B, and Audigier Y
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- Animals, Apelin Receptors, Arterioles metabolism, In Situ Hybridization, Ligands, Mice, Mice, Inbred C57BL, Phenotype, RNA Probes, Receptors, G-Protein-Coupled genetics, Retinal Vein metabolism, Biomarkers analysis, Ephrin-B2 metabolism, Receptor, EphB4 metabolism, Receptors, G-Protein-Coupled metabolism, Retinal Vein growth & development
- Abstract
Expression of the new G protein-coupled msr/apj receptor in the mouse embryo is restricted to the endothelial layer of the primary blood vessels and the newly forming heart (Mech. Dev. 84 (1999) 199). During development of the retinal vasculature, the msr/apj gene is not expressed throughout the vascular network, indicating a possible relationship between the localization of expression and the acquisition of arterial or venous identity (Mech. Dev. 110 (2002) 183). Here we first established that retinal expression of ephrin-B2 and its putative receptor EphB4 correlates with arterial and venous phenotype, respectively. Then we analyzed the expression pattern of msr/apj in the retinal vessels at various stages of postnatal development by in situ hybridization. In contrast to the expression of ephrin-B2 or EphB4, msr/apj transcripts can be detected as early as postnatal day P3. From P3 to P12, msr/apj expression in the vascular network is restricted to the venules and the associated capillaries. The msr/apj gene is thus an early and specific marker of the venous phenotype in the retinal vasculature.
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- 2003
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16. Apelin (65-77) activates extracellular signal-regulated kinases via a PTX-sensitive G protein.
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Masri B, Lahlou H, Mazarguil H, Knibiehler B, and Audigier Y
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- Adipokines, Animals, Apelin, Apelin Receptors, CHO Cells, Cricetinae, Cyclic AMP-Dependent Protein Kinases chemistry, Dose-Response Relationship, Drug, Endothelium metabolism, Enzyme Activation, Enzyme Inhibitors pharmacology, Flavonoids pharmacology, Genes, Dominant, Immunoblotting, Indoles pharmacology, Intercellular Signaling Peptides and Proteins, Maleimides pharmacology, Mice, Mitogen-Activated Protein Kinase 1 metabolism, Mitogen-Activated Protein Kinase 3, Monomeric GTP-Binding Proteins metabolism, Mutation, Peptide Fragments chemistry, Phosphorylation, Plasmids metabolism, Protein Binding, Protein Isoforms, Protein Structure, Tertiary, Receptors, Cell Surface biosynthesis, Receptors, Dopamine D2 biosynthesis, Signal Transduction, Time Factors, Transfection, Type C Phospholipases metabolism, Carrier Proteins chemistry, Carrier Proteins metabolism, GTP-Binding Proteins metabolism, Mitogen-Activated Protein Kinases metabolism, Pertussis Toxin, Receptors, G-Protein-Coupled, Recombinant Proteins, Virulence Factors, Bordetella metabolism
- Abstract
We report here that apelin (65-77) induces activation of extracellular-regulated kinases (ERKs) in Chinese hamster ovary (CHO) cells expressing the msr/apj receptor. This concentration-dependent activation was transient, peaking at 5 min. Pretreatment of CHO cells with pertussis toxin fully abrogated ERK phosphorylation, whereas overexpression of the beta-adrenergic receptor kinase-1 C-terminal fragment did not alter ERK activation. Transfection with a dominant-negative mutant of Ras was without effect on ERK activation, whereas an inhibitor of many protein kinase C isoforms, GF109203X, strongly decreased it. These results demonstrate that stimulation of the murine msr/apj receptor promotes ERK activation via the alpha subunit of a pertussis toxin-sensitive protein in a Ras-independent pathway., ((c)2002 Elsevier Science.)
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- 2002
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17. Expression of the murine msr/apj receptor and its ligand apelin is upregulated during formation of the retinal vessels.
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Saint-Geniez M, Masri B, Malecaze F, Knibiehler B, and Audigier Y
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- Adipokines, Animals, Apelin, Apelin Receptors, Gene Expression Regulation, Developmental, In Situ Hybridization, Intercellular Signaling Peptides and Proteins, Ligands, Mice, Mice, Inbred C57BL, Retinal Vessels metabolism, Up-Regulation, Carrier Proteins genetics, Receptors, Cell Surface genetics, Receptors, Dopamine D2 genetics, Receptors, G-Protein-Coupled, Retinal Vessels growth & development
- Abstract
We have recently identified a new G protein-coupled receptor, msr/apj, whose transcripts are detected in the endothelium of the primary blood vessels and the newly forming heart (Mech. Dev. 1999;84:199). Its expression during formation of the embryonic vasculature incited us to investigate whether expression of the receptor also increased during the formation of retinal vessels, which occurs postnatally in the mouse. Interestingly, msr/apj transcripts are indeed associated with the forming vessels and trace the centrifugal extension of the superficial vasculature. We also show that expression of the endogenous ligand apelin is upregulated at the leading edge of vessel formation.
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- 2002
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18. Amino acid sequence and embryonic expression of msr/apj, the mouse homolog of Xenopus X-msr and human APJ.
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Devic E, Rizzoti K, Bodin S, Knibiehler B, and Audigier Y
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- Amino Acid Sequence, Animals, Apelin Receptors, Blood Vessels embryology, Blood Vessels metabolism, Cardiovascular System embryology, Cloning, Molecular, Endothelium, Vascular embryology, Endothelium, Vascular metabolism, Humans, In Situ Hybridization, Limb Buds metabolism, Mice, Molecular Sequence Data, Receptor Protein-Tyrosine Kinases genetics, Receptors, Cell Surface metabolism, Receptors, Dopamine D2 genetics, Receptors, Growth Factor genetics, Receptors, Vascular Endothelial Growth Factor, Sequence Analysis, DNA, Sequence Homology, Amino Acid, Gene Expression Regulation, Developmental, Receptors, Cell Surface genetics, Receptors, G-Protein-Coupled, Xenopus Proteins
- Abstract
We have recently identified a new G protein-coupled receptor, X-msr, whose expression is associated with the endothelial lineage in Xenopus laevis (Devic, E., Paquereau, L., Vernier, P., Knibiehler, B., Audigier, Y., 1996. Expression of a new G protein-coupled receptor X-msr is associated with an endothelial lineage in Xenopus laevis. Mech. Dev. 59, 129-140). Based on its structural analogy to the human orphan receptor APJ, we cloned the murine msr/apj receptor and analyzed its expression in developing tissues. As observed for X-msr, msr/apj transcripts are detected in the endothelium of the primary blood vessels and the forming heart. In addition, they are expressed in somites, limb bud and branchial arches. This expression pattern is distinct from that of the Flk1 gene and suggests that the msr/apj gene is expressed in a subpopulation of endothelial precursors and a mesenchymal population derived from paraaxial mesoderm.
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- 1999
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19. A constitutively activated mutant of galphaq down-regulates EP-cadherin expression and decreases adhesion between ectodermal cells at gastrulation.
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Rizzoti K, Paquereau L, Shaw A, Knibiehler B, and Audigier Y
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- Animals, Cadherins metabolism, Cell Adhesion genetics, Down-Regulation, Embryo, Nonmammalian metabolism, GTP-Binding Proteins metabolism, Gene Expression Regulation, Developmental, Microinjections, Mutation, Phenotype, RNA, Messenger, Xenopus Proteins, Xenopus laevis genetics, Cadherins genetics, Ectoderm cytology, GTP-Binding Proteins genetics, Gastrula physiology, Xenopus laevis embryology
- Abstract
We have examined the expression and function of the heterotrimeric GTP-binding protein Gq during early Xenopus embryogenesis. Abundant XGalphaq transcripts were detected in oocytes and early embryos by Northern blot analysis. In situ hybridization revealed that these transcripts are confined to the animal hemisphere of the mature oocyte and to the presumptive ectoderm of cleaving embryos. Microinjection at the two-cell stage of alphaq and Q209Lalphaq, a constitutively activated mutant, causes a disruption in ectodermal cell adhesion at late gastrulation. Dissociation/reaggregation experiments performed on animal cap explants clearly demonstrate that the Q209Lalphaq-induced phenotype occurs after reaggregation of the explants with a time-course similar to that observed in whole embryos. RT-PCR experiments performed on the explants from Q209Lalphaq-injected embryos revealed a selective decrease in the amount of EP-cadherin mRNA. Co-injection of EP-cadherin RNA, but also E-cadherin RNA, rescued the disaggregated phenotype. These data emphasize the functional link between Gq protein-coupled signalling pathways and cadherin molecules in the ectodermal layer during the morphogenetic movements of gastrulation., (Copyright 1998 Elsevier Science Ireland Ltd. All rights reserved.)
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- 1998
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20. Expression of a new G protein-coupled receptor X-msr is associated with an endothelial lineage in Xenopus laevis.
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Devic E, Paquereau L, Vernier P, Knibiehler B, and Audigier Y
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- Amino Acid Sequence, Animals, Apelin Receptors, Base Sequence, Cloning, Molecular, Endothelium chemistry, Gene Expression Regulation, Developmental, In Situ Hybridization, Kinetics, Larva chemistry, Molecular Sequence Data, Receptors, Cell Surface genetics, Sequence Analysis, DNA, Receptors, Cell Surface chemistry, Receptors, G-Protein-Coupled, Xenopus Proteins, Xenopus laevis embryology
- Abstract
In order to determine whether G protein-coupled receptors play a role in early embryogenesis, we looked for cDNA fragments amplified between primers located in consensus sequences of transmembrane segments. Using one such amplified fragment as a probe, we cloned a novel member of the G protein-coupled receptor superfamily in Xenopus. Alignment of the deduced protein sequence with that of other receptors discloses some homology with angiotensin receptors. A single transcript of 2.5 kb is detected at the late blastula stage and its expression increases during gastrulation. In situ hybridization reveals transcripts initially in the ventrolateral involuting marginal zone and later in the lateral plate mesoderm. At larval stages, the transcript is expressed in procardiac tube and forming blood vessels, where it is localized in the inner endothelial layer. Thus, this gene traces an endothelial lineage and represents a very early and unique marker in Xenopus of the specification of cardiac and vascular endothelia. We propose the name of X-msr for mesenchyme-associated serpentine receptor.
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- 1996
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21. The mRNA encoding a beta subunit of heterotrimeric GTP-binding proteins is localized to the animal pole of Xenopus laevis oocyte and embryos.
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Devic E, Paquereau L, Rizzoti K, Monier A, Knibiehler B, and Audigier Y
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- Amino Acid Sequence, Animals, Base Sequence, Blotting, Northern, Cloning, Molecular, DNA, Complementary chemistry, Molecular Sequence Data, Oogenesis, Protein Conformation, GTP-Binding Proteins genetics, Oocytes chemistry, RNA, Messenger metabolism, Xenopus laevis embryology
- Abstract
In order to provide evidence for a potential role of heterotrimeric GTP-binding proteins in the transduction of developmental signals, we prepared cDNAs from Xenopus laevis embryos and looked for fragments amplified between primers located in conserved sequences of the different subtypes of beta subunit. Using the amplified fragment as a probe, we cloned a member of the beta subunit family. The deduced protein sequence of the amphibian cDNA is highly homologous to the beta 1 subtype and, accordingly, we have named the Xenopus gene XG beta 1. In situ hybridization and RNase protection assay revealed that XG beta 1 mRNA is confined to the animal hemisphere of the mature oocyte. This localization of XG beta 1 mRNA is established at stage V during oogenesis. Following fertilization, the maternal mRNAs cosegregate with animal cells during cleavage stages. At gastrulation, transcripts are expressed in the dorsal ectoderm layer that will give rise to the central nervous system. Thus, XG beta 1 mRNA belongs to the small family of localized maternal mRNAs; as a transducing protein, its restriction to a subset of embryonic cells could mediate the distinct responsiveness which contributes to the patterning of the embryo.
- Published
- 1996
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22. Collagen type IV of Drosophila is stockpiled in the growing oocyte and differentially located during early stages of embryogenesis.
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Knibiehler B, Mirre C, and Le Parco Y
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- Animals, Collagen genetics, Drosophila melanogaster embryology, Immunohistochemistry, Nucleic Acid Hybridization, Oocytes cytology, Collagen metabolism, Drosophila melanogaster metabolism, Gene Expression Regulation physiology, Oocytes metabolism
- Abstract
We have developed and characterized a battery of specific polyclonal antibodies directed against specific portions of the alpha-chain of collagen type IV synthesized in Drosophila by the gene DCg1. Here, we describe the use of these antibodies together with in situ hybridization experiments in an attempt to study the expression and localization of collagen type IV during Drosophila oogenesis and early embryogenesis. The results clearly demonstrate that DCg1 is maternally expressed by follicle cells and that the collagen type IV chain produced is stockpiled in the growing oocyte. During the gastrulation stages, this component of Drosophila basement membranes concentrated on cells involved in the gradual invaginations leading to morphogenetic furrows. The presence of collagen type IV, which is an RGD-bearing molecule, during early stages of Drosophila development is discussed in comparison with the crucial, active role its vertebrate counterpart is supposed to play in morphogenetic processes.
- Published
- 1990
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23. Haemocytes accumulate collagen transcripts during Drosophila melanogaster metamorphosis.
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Knibiehler B, Mirre C, Cecchini J-, and Le Parco Y
- Abstract
We report a direct examination of the expression of one collagen gene (DCg1) during Drosophila melanogaster metamorphosis, based on data from in situ hybridization. The transcripts of this gene, thought to encode a basement membrane type IV collagen, are mainly accumulated during ecdysis in wandering haemocytes. Our results demonstrate that haemocytes contribute to extracellular matrix deposition and seem to perform a fibroblastic function during Drosophila development.
- Published
- 1987
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24. Localization of ribosomal cistrons in the quail oocyte during meiotic prophase I.
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Knibiehler B, Navarro A, Mirre C, and Stahl A
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- Animals, Cell Nucleolus ultrastructure, Chromosome Mapping, Coturnix, Female, Prophase, Chromosomes ultrastructure, Genes, Meiosis, Oocytes ultrastructure, Ovum ultrastructure, RNA, Ribosomal genetics
- Published
- 1977
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25. A re-evaluation of the relationships between the fibrillar centres and the nucleolus-organizing regions in reticulated nucleoli: ultrastructural organization, number and distribution of the fibrillar centres in the nucleolus of the mouse Sertoli cell.
- Author
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Mirre C and Knibiehler B
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- Animals, Genes, Male, Mice, Microscopy, Electron, Nucleic Acid Hybridization, Nucleolus Organizer Region ultrastructure, RNA, Bacterial, RNA, Ribosomal, Cell Nucleolus ultrastructure, Sertoli Cells ultrastructure
- Abstract
In mouse testis, the diploid Sertoli cell displays one large nucleolus flanked symmetrically by two heterochromatic masses. The hybridization in situ with [3H]rRNA confirmed that the ribosomal cistrons are localized with in the central nucleolar mass. At the ultrastructural level this nucleolar mass appears to be reticulated and contains numerous fibrillar centres. These fibrillar centres are surrounded and interconnected by an electron-opaque fibrillar network, which constitutes the reticulated nucleolonema of the nucleolus. Ag--NOR staining reveals the presence of the argyrophilic proteins associated with active nucleolus-organizing regions (NORs) within both the fibrillar centres and the electron-opaque fibrillar component. Autoradiographic studies after [3H]uridine incorporation show that ribosomal DNA transcription only takes place in this dense fibrillar component. Three-dimensional reconstruction of four Sertoli cell nucleoli after serial sectioning reveals that the size and number of the fibrillar centers are very variable from one cell to another (26, 35, 38 an 41 fibrillar centres). The analysis of the volume occupied by the fibrillar centres as compared to the whole nucleolar volume demonstrates that the larger the nucleolus, the more fibrillar centres it contains, but also the more numerous the fibrillar centres, the larger their total volume. While in each case the number of the NORs is virtually the same, i.e. ten. In the light of these results we concluded that, at least in reticulated nucleoli, there is no numerical relationship between the number of fibrillar centres and the number of NORs, and that the fibrillar centers cannot be considered only as the nucleolar counterparts of the NORs. Moreover, the increasing number of fibrillar centres from the smallest nucleolus to the largest one is difficult to explain by the previously postulated hypothesis of a reserve of inactive rDNA packaged in the fibrillar centers. These data led us to reconsider the role of the fibrillar centres in the transcriptional activity of reticulated nucleoli.
- Published
- 1982
- Full Text
- View/download PDF
26. Characterization and expression of collagen-like genes in Drosophila melanogaster.
- Author
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Le Parco Y, Cecchini JP, Knibiehler B, and Mirre C
- Subjects
- Animals, Base Sequence, Chickens, DNA genetics, DNA isolation & purification, DNA Restriction Enzymes, DNA, Recombinant, Nucleic Acid Hybridization, Collagen genetics, Drosophila melanogaster genetics, Gene Expression Regulation
- Abstract
We have used a cloned chicken collagen cDNA sequence to help identify hypothetic members of the collagen gene family from Drosophila melanogaster. Several experimental evidences have been obtained which indicate that the Drosophila genome contains numerous collagen-like sequences. We have characterized in more detail ten distinct DNA sequences that hybridized strongly to the heterologous collagen probe. By in situ hybridization we have shown that these sequences are dispersed throughout the Drosophila genome. Two of them are shown to originate from the previously described DCg 1 and DCg 2 collagen genes. In other respects, we show that in addition to DCg 1 and DCg 2, at least five putative collagen genes are expressed during the Drosophila lifetime. These genes are unique, and some of them are seen to be transcribed into different size classes of mRNAs. Additionally, the data presented so far demonstrate that the expression of these genes is regulated temporally and/or quantitatively during the Drosophila life cycle.
- Published
- 1986
- Full Text
- View/download PDF
27. Nucleolar organizer structure and activity in a nucleolus without fibrillar centres: the nucleolus in an established Drosophila cell line.
- Author
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Knibiehler B, Mirre C, and Rosset R
- Subjects
- Animals, Cell Line, Cell Nucleolus metabolism, Chromatin ultrastructure, DNA-Directed RNA Polymerases metabolism, Drosophila, Edetic Acid, Microscopy, Electron, RNA biosynthesis, Cell Nucleolus ultrastructure, Nucleolus Organizer Region ultrastructure
- Abstract
Classical electron-microscopic techniques (enzymic digestion, EDTA regressive staining) allied with autoradiographic studies after [3H]uridine incorporation or after RNA synthesis initiated by an exogeneous RNA polymerase in the presence of tritiated GTP, enabled us to describe the fine structure and activity of the nucleolus in an established Drosophila cell line. This nucleolus is composed of a large central multilobed core containing proteins, RNA molecules and a DNA-containing component. This core is surrounded by and connected to large clumps of dense fibrillar nucleolus-associated chromatin, which are intermingled with fibrillogranular ramifications extending from the core towards the nuclear envelope. These ramifications are covered by granules of ribosomal ribonucleoprotein. As shown by EDTA regressive staining the nucleolar core contains a ribonucleoprotein network, which unravels and ramifies within a fibrous matrix. RNA synthesis takes place at the level of this network in the internal part of the core. The molecules synthesized are associated with proteins and are exported out of the core in the form of granules. Although it is composed of the same constituents as other nucleoli, the nucleolus of Drosophila cells seems to be less organized, in that it never displays fibrillar centres, which have been referred to as the nucleolar counterparts of the nucleolus-organizers in a wide variety of organisms.
- Published
- 1982
- Full Text
- View/download PDF
28. De novo expression of a type IV collagen gene in Drosophila embryos is restricted to mesodermal derivatives and occurs at germ band shortening.
- Author
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Mirre C, Cecchini JP, Le Parco Y, and Knibiehler B
- Subjects
- Animals, Autoradiography, DNA, Drosophila melanogaster, Mesoderm physiology, Nucleic Acid Hybridization, Time Factors, Collagen genetics, Genes
- Abstract
We have examined directly the expression of one collagen gene (DCg1) during Drosophila melanogaster embryogenesis by means of in situ hybridization. Transcripts of this gene, which were demonstrated to encode a basement membrane type IV collagen chain, began to accumulate specifically in mesodermal derivatives at stages 12-13 of embryogenesis, and not before. Cells expressing this gene overlap, or are closely intermingled with, somatic and visceral mesoderm in stages 12-14. In stages 15-17, in addition to the strongly positive fat bodies, highly labelled cell spots are found scattered around all the parts of the gut and symmetrically on each side of the ventral nerve cord. They correspond to circulating mesodermal cells which we consider to be haemocytes or mesoblasts.
- Published
- 1988
- Full Text
- View/download PDF
29. Multiplication of nucleolar fibrillar centres and absence of rDNA amplification in mouse oocyte during meiotic prophase I.
- Author
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Knibiehler B, Mirre C, and Stahl A
- Subjects
- Animals, Cell Nucleolus metabolism, DNA, Ribosomal, Female, Genes, Mice, Microscopy, Electron, Nucleolus Organizer Region ultrastructure, Oocytes metabolism, RNA, Ribosomal biosynthesis, Transcription, Genetic, Cell Nucleolus ultrastructure, DNA genetics, Meiosis, Oocytes ultrastructure, Oogenesis, Ovum ultrastructure
- Abstract
During meiotic prophase I the nucleolus of the mouse oocyte assumes a reticulate structure of 'nucleolonema' type. This change coincides with the appearance of several secondary fibrillar centres. The number of these centres at diplotene (97-113), largely exceeds that of nucleolar organizers (4c DNA = 20 NORs). The quantitative analysis of autoradiographs after hybridization in situ with 3H-uridine labelled rRNA, enabled us to demonstrate that the multiplication of the fibrillar centres in mouse oocyte nucleolus during meiotic prophase I is not the result of an amplification of the rDNA. The number of silver grains in pachytene and diplotene nuclei was twice that counted for somatic cell and oogonium nuclei (2c DNA).
- Published
- 1983
- Full Text
- View/download PDF
30. Ultrastructural and functional variations in the spermatid nucleolus during spermiogenesis in the mouse.
- Author
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Mirre C and Knibiehler B
- Subjects
- Animals, Cell Nucleolus physiology, Male, Mice, Microscopy, Electron, Nucleolus Organizer Region physiology, Spermatids physiology, Cell Nucleolus ultrastructure, Nucleolus Organizer Region ultrastructure, Spermatids ultrastructure, Spermatogenesis
- Abstract
The localization, structure, and activity of the nucleolus-organizers (NORs) were studied during spermiogenesis in the mouse by light and electron microscopy procedures including NOR-silver-staining and actinomycin D treatment. After the two meiotic divisions the NORs resume their activity during the Golgi phase of spermatid differentiation (steps 1-3), and the nucleolus displays a specific 'padlock' structure containing the fibrillar components of an active nucleolus. This activity drops during the cap phase (steps 4-7) during which the nucleolus undergoes a segregation process of its components. No nucleolar structure is visible during the acrosomal and maturation phases of spermatid differentiation.
- Published
- 1985
- Full Text
- View/download PDF
31. Evidence for a type-IV-related collagen in Drosophila melanogaster. Evolutionary constancy of the carboxyl-terminal noncollagenous domain.
- Author
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Cecchini JP, Knibiehler B, Mirre C, and Le Parco Y
- Subjects
- Animals, Base Sequence, Biological Evolution, DNA, Genetic Code, Humans, Mice, Protein Conformation, Species Specificity, Collagen genetics, Drosophila melanogaster genetics
- Abstract
Type IV collagen, a major structural component of basement membrane, has been characterized only in vertebrates. It is unique among the collagenous proteins in that it forms specific lattice networks by end-to-end interactions. In particular, in mammals the C-terminal noncollagenous domain (NCl) of collagen IV was shown to be one of the major cross-linking sites in the network assembly. Here, we give the first direct evidence of type-IV-related collagen in invertebrates by sequence analysis of cDNA and genomic DNA clones for the 3'-end of a previously characterized Drosophila collagen gene. The data describe the C-terminal 190 amino acid residues of the triple helix and the entire noncollagenous domain (231 amino acids) of the chain encoded for by this gene. Comparison with data reported for human and mouse alpha 1(IV) chains reveals that triple-helix regions are quite different, while NC1 structures are very similar. This suggests different constraints on triple-helix and NC1 domains during evolution. Present data support the assumption that the NC1 structure originated from duplication of an ancestral sequence; the extent of both interspecies and intramolecular homologies suggests the maintenance in vertebrates and invertebrates of an ancestral specific function.
- Published
- 1987
- Full Text
- View/download PDF
32. Stage and tissue-specific expression of a collagen gene during Drosophila melanogaster development.
- Author
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Le Parco Y, Knibiehler B, Cecchini JP, and Mirre C
- Subjects
- Animals, DNA Restriction Enzymes, Drosophila melanogaster cytology, Drosophila melanogaster growth & development, Nucleic Acid Hybridization, RNA, Messenger genetics, RNA, Messenger isolation & purification, Transcription, Genetic, Collagen genetics, Drosophila melanogaster genetics, Genes
- Abstract
Based on data from developmental RNA profiles and in situ hybridization, we report a direct examination of the expression of one collagen gene (Dcg1) during drosophila melanogaster life cycle. These studies show, for the first time, that the expression of a collagen gene is both differential and tissue-specific during the course of development. Moreover, they demonstrate that the connective tissues in Drosophila do contain a collagen type synthesized by mesodermal tissues. Indeed the accumulation of Dcg1 transcripts was located mainly within the second instar fat bodies, the third instar lymph glands, and over adepithelial cells associated with third instar imaginal discs. In addition, these results seem to confirm the interpretation that wandering hemocytes released by the lymph glands could contribute in extracellular matrix composition in some tissues in the larva.
- Published
- 1986
- Full Text
- View/download PDF
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