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R Chiquet-Ehrismann

Publications and source records attributed to R Chiquet-Ehrismann.

At least 19 recordsLinked to original sources
PubMed2006

Phylogenetic analysis of the tenascin gene family: evidence of origin early in the chordate lineage.

BACKGROUND: Tenascins are a family of glycoproteins found primarily in the extracellular matrix of embryos where they help to regulate cell proliferation, adhesion and migration. In order to learn more about their origins and relationships to each other, as well as to clarify the nomenclature used to describe them, the tenascin genes of the urochordate Ciona intestinalis, the pufferfish Tetraodon nigroviridis and Takifugu rubripes and the frog Xenopus tropicalis were identified and their gene organization and predicted protein products compared with the previously characterized tenascins of amniotes. RESULTS: A single tenascin gene was identified in the genome of C. intestinalis that encodes a polypeptide with domain features common to all vertebrate tenascins. Both pufferfish genomes encode five tenascin genes: two tenascin-C paralogs, a tenascin-R with domain organization identical to mammalian and avian tenascin-R, a small tenascin-X with previously undescribed GK repeats, and a tenascin-W. Four tenascin genes corresponding to tenascin-C, tenascin-R, tenascin-X and tenascin-W were also identified in the X. tropicalis genome. Multiple sequence alignment reveals that differences in the size of tenascin-W from various vertebrate classes can be explained by duplications of specific fibronectin type III domains. The duplicated domains are encoded on single exons and contain putative integrin-binding motifs. A phylogenetic tree based on the predicted amino acid sequences of the fibrinogen-related domains demonstrates that tenascin-C and tenascin-R are the most closely related vertebrate tenascins, with the most conserved repeat and domain organization. Taking all lines of evidence together, the data show that the tenascins referred to as tenascin-Y and tenascin-N are actually members of the tenascin-X and tenascin-W gene families, respectively. CONCLUSION: The presence of a tenascin gene in urochordates but not other invertebrate phyla suggests that tenascins may be specific to chordates. Later genomic duplication events led to the appearance of four family members in vertebrates: tenascin-C, tenascin-R, tenascin-W and tenascin-X.

Animals↗
PubMed2006

Teneurins: a conserved family of transmembrane proteins involved in intercellular signaling during development.

Teneurins, which were initially described as ten-a and the pair-rule gene ten-m/odz in Drosophila, are a family of highly conserved proteins that have recently been characterized in Caenorhabditis elegans and a number of vertebrates. We have proposed the nomenclature teneurin 1-4 for the four members of this gene family found in vertebrates. Recent evidence shows that teneurins belong to a novel class of signaling molecules that function both at the cell surface as type II transmembrane receptors and, after the release of the intracellular domain, as transcriptional regulators. Nuclear localization of the intracellular domain has been observed in vitro in mammalian cells and confirmed in vivo in C. elegans. RNAi studies and mutational analysis has revealed that Ten-1 in C. elegans is an important regulator of many aspects of morphogenesis, including germ cell development and neuronal pathfinding. In vertebrates, teneurins are concentrated in the developing and adult central nervous system and at sites of pattern formation, including the developing limb. Teneurins also possess a carboxy terminal sequence that may be processed to generate a neuromodulatory peptide. Teneurin function appears to be required for a fundamentally important signaling mechanism conserved between invertebrates and vertebrates having an impact on many processes relying on cell-cell contact throughout development.

Animals↗
PubMed2004

Murine tenascin-W: a novel mammalian tenascin expressed in kidney and at sites of bone and smooth muscle development.

We cloned and characterized a novel member of the tenascin family of extracellular matrix proteins--the murine orthologue of zebrafish tenascin-W. Full-length recombinant tenascin-W was expressed and purified from mammalian cell cultures. Rotary shadowing followed by electron microscopy showed that tenascin-W forms hexabrachions. We studied its expression during development and in the adult by immunohistochemistry, in situ hybridization and immunoblotting. Tenascin-W is expressed during palate formation, osteogenesis and smooth muscle development. In the adult, tenascin-W is found in the kidney, cardiac semilunar valves, corneal limbus and periosteum. Tenascin-W and tenascin-C expression overlap in many of these areas. Bone-morphogenic-protein-2 treated C2C12 cells secrete tenascin-W and are able to adhere to and to extend actin-rich processes on a tenascin-W substratum. In vitro, cells bind to tenascin-W in an RGD-dependent manner. This adhesion is increased by transfection of alpha8 integrin, which localizes with tenascin-W in the periosteum and kidney.

Amino Acid Sequence↗
PubMed2001

Interference of tenascin-C with syndecan-4 binding to fibronectin blocks cell adhesion and stimulates tumor cell proliferation.

Tenascin-C is an adhesion-modulatory extracellular matrix molecule that is highly expressed in tumors. To investigate the effect of tenascin-C on tumor cells, we analyzed its antiadhesive nature and effect on tumor cell proliferation in a fibronectin context. Glioblastoma and breast carcinoma cell adhesion was compromised by a mixed fibronectin/tenascin-C substratum, which concomitantly caused increased tumor-cell proliferation. We identified the antiadhesive mechanism as a specific interference of tenascin-C with cell binding to the HepII/syndecan-4 site in fibronectin through direct binding of tenascin-C to the 13th fibronectin type III repeat (FNIII13). Cell adhesion and proliferation levels were restored by the addition of FNIII13. Overexpression of syndecan-4, but not syndecan-1 or -2, reverted the cell adhesion defect of tenascin-C. We characterized FNIII13 as the binding site for syndecan-4. Thus we describe a novel mechanism by which tenascin-C impairs the adhesive function of fibronectin through binding to FNIII13, thereby inhibiting the coreceptor function of syndecan-4 in fibronectin-induced integrin signaling.

Animals↗
PubMed2001

Tenascin-Y is concentrated in adult nerve roots and has barrier properties in vitro.

Several molecules have been identified as potential sources of the barriers to glial cell mixing and sensory regeneration that exist at the boundary between the peripheral and central nervous systems, including tenascin-C, tenascin-R, chondroitin sulfate proteoglycans, and NG2. Here we show that tenascin-Y, the avian homologue of tenascin-X, is concentrated in the proximal portions of peripheral nerves in the chicken. In vitro analyses of cultures enriched for Schwann cells demonstrate that recombinant tenascin-Y has dose-dependent effects on glial cell attachment, spreading, and migration. In addition, nanomolar concentrations of tenascin-Y cause the rapid collapse of sensory growth cones cultured on fibronectin, and regenerating sensory neurites preferentially migrate on fibronectin and avoid tenascin-Y in microstripe assays. We conclude that the expression pattern of tenascin-Y and its properties in vitro are consistent with a role as an inhibitor of glial cell migration and sensory regeneration in nerve roots.

Animals↗
PubMed2001

Dermal fibroblast-derived growth factors restore the ability of beta(1) integrin-deficient embryonal stem cells to differentiate into keratinocytes.

Embryonal stem (ES) cells that are homozygous null for the beta(1) integrin subunit fail to differentiate into keratinocytes in vitro but do differentiate in teratomas and wild-type/beta(1)-null chimeric mice. The failure of beta(1)-null ES cells to differentiate in culture might be the result of defective extracellular matrix assembly or reduced sensitivity to soluble inducing factors. By culturing embryoid bodies on dead, deepidermized human dermis (DED) we showed that epidermal basement membrane did not induce beta(1)-null ES cells to undergo keratinocyte differentiation and did not stimulate the differentiation of wild-type ES cells. Coculture with epidermal keratinocytes also had no effect. However, when human dermal fibroblasts were incorporated into DED, the number of epidermal cysts formed by wild-type ES cells increased dramatically, and small groups of keratin 14-positive cells differentiated from beta(1)-null ES cells. Fibroblast-conditioned medium stimulated differentiation of K14-positive cells in wild-type and beta(1)-null embryoid bodies. Of a range of growth factors tested, KGF, FGF10, and TGFalpha all stimulated differentiation of keratin 14-positive beta(1)-null cells, and KGF and FGF10 were shown to be produced by the fibroblasts used in coculture experiments. The effects of the growth factors on wild-type ES cells were much less pronounced, suggesting that the concentrations of inducing factors already present in the medium were not limiting for wild-type cells. We conclude that the lack of beta(1) integrins decreases the sensitivity of ES cells to soluble factors that induce keratinocyte differentiation.

3T3 Cells↗
PubMed2001

Teneurin-2 is expressed in tissues that regulate limb and somite pattern formation and is induced in vitro and in situ by FGF8.

Teneurin-2 is a member of a novel family of transmembrane proteins characterized to date in fish, birds, mammals, and Drosophila (e.g., the pair-rule gene product Ten-m). We have shown that teneurin-2 is expressed by neurons in the developing avian visual system in a pattern complementary to the expression of teneurin-1 and that recombinant teneurin-2 induces morphologic changes in neuronal cells in culture (Rubin et al., 1999). Here we have used cRNA probes to two newly identified splice variants and a teneurin-2-specific antibody to determine whether teneurin-2 is also expressed outside the nervous system. Both reverse transcriptase-polymerase chain reaction and in situ hybridization indicate that the three splice variants known so far are coexpressed at sites of pattern formation during development. Teneurin-2 mRNAs and protein are found in the developing limbs, somites, and craniofacial mesenchyme. In addition to expression of teneurin-2 by the apical ectodermal ridge, teneurin-2 transcripts also appear transiently at sites of tendon development. Teneurin-2 expression patterns were strikingly similar to those of fibroblast growth factor 8 (FGF8). In agreement with the overlapping expression pattern, FGF8-coated beads implanted into chicken limb buds induced the ectopic expression of teneurin-2 and soluble FGF8 induced teneurin-2 in limb explant cultures. Thus, teneurin-2 could act downstream of FGF8 during morphogenesis.

Alternative Splicing↗
PubMed2000

CALEB binds via its acidic stretch to the fibrinogen-like domain of tenascin-C or tenascin-R and its expression is dynamically regulated after optic nerve lesion.

Recently, we described a novel chick neural transmembrane glycoprotein, which interacts with the extracellular matrix proteins tenascin-C and tenascin-R. This protein, termed CALEB, contains an epidermal growth factor-like domain and appears to be a novel member of the epidermal growth factor family of growth and differentiation factors. Here we analyze the interaction between CALEB and tenascin-C as well as tenascin-R in more detail, and we demonstrate that the central acidic peptide segment of CALEB is necessary to mediate this binding. The fibrinogen-like globe within tenascin-C or -R enables both proteins to bind to CALEB. We show that two isoforms of CALEB in chick and rodents exist that differed in their cytoplasmic segments. To begin to understand the in vivo function of CALEB and since in vitro antibody perturbation experiments indicated that CALEB might be important for neurite formation, we analyzed the expression pattern of the rat homolog of CALEB during development of retinal ganglion cells, after optic nerve lesion and during graft-assisted retinal ganglion cell axon regeneration by in situ hybridization. These investigations demonstrate that CALEB mRNA is dynamically regulated after optic nerve lesion and that this mRNA is expressed in most developing and in one-third of the few regenerating (GAP-43 expressing) retinal ganglion cells.

Amino Acid Sequence↗
PubMed2000

Phylogenetic analysis of teneurin genes and comparison to the rearrangement hot spot elements of E. coli.

Teneurins are a novel family of transmembrane proteins conserved between invertebrates and vertebrates. There are two members in Drosophila, one in C. elegans and four members in mouse. Here, we describe the analysis of the genomic structure of the human teneurin-1 gene. The entire human teneurin-1 (TEN1) gene is contained in eight PAC clones representing part of the chromosomal locus Xq25. Interestingly, many X-linked mental retardation syndromes (XLMR) and non-specific mental retardation (MRX) are mapped to this region. The location of the human TEN1 together with the neuronal expression makes TEN1 a candidate gene for XLMR and MRX. We also identified large parts of the human teneurin-2 sequence on chromosome 5 and sections of human teneurin-4 at chromosomal position 11q14. Database searches resulted in the identification of ESTs encoding parts of all four human members of the teneurin family. Analysis of the genomic organization of the Drosophila ten-a gene revealed the presence of exons encoding a long form of ten-a, which can be aligned with all other teneurins known. Sequence comparison and phylogenetic trees of teneurins show that insects and vertebrates diverged before the teneurin ancestor was duplicated independently in the two phyla. This is supported by the presence of conserved intron positions between teneurin genes of man, Drosophila and C. elegans. It is therefore not possible to class any of the vertebrate teneurins with either Drosophila Ten-a or Ten-m. The C-terminal part of all teneurins harbours 26 repetitive sequence motifs termed YD-repeats. YD-repeats are most similar to the repeats encoded by the core of the rearrangement hot spot (rhs) elements of Escherichia coli. This makes the teneurin ancestor a candidate gene for the source of the rhs core acquired by horizontal gene transfer.

Amino Acid Sequence↗
PubMed2000

Tenascin-C induced stimulation of chondrogenesis is dependent on the presence of the C-terminal fibrinogen-like globular domain.

The relationship between structure of tenascin-C (Tn-C), a multi-domain extracellular matrix protein, and its stimulation of chondrogenesis was examined using recombinant Tn-C isoforms (full length or with specific domains deleted) as substrata for undifferentiated chicken mesenchymal cells. Of the Tn-C variants tested, only Tn-C lacking the fibrinogen-like domain or Tn-C comprised solely of fibrinogen-like domains failed to stimulate chondrogenesis. The ability of variants to stimulate chondrogenesis was not dependent on their ability to support adhesion or stimulate proliferation. These results demonstrate that the fibrinogen-like domain of Tn-C is necessary but not sufficient for induction of chondrogenesis.

Animals↗
PubMed2000

Expression patterns of two new members of the Semaphorin family in Drosophila suggest early functions during embryogenesis.

We report the sequence and expression analysis of two new Drosophila members of the Semaphorin family. Both proteins show the presence of Semaphorin domains and transmembrane domains. Both genes are expressed maternally and in embryos, and reveal distinct expression patterns much earlier than the onset of neurogenesis. We also present an overview of the domain structure of all so far known semaphorins in Drosophila. Furthermore, we compared all Drosophila and C. elegans Semaphorins and discuss them in the light of their evolution.

Amino Acid Sequence↗
PubMed2000

Lactogenic hormones and tenascin-C regulate C/EBPalpha and beta in mammary epithelial cells.

Mammary epithelial cell differentiation depends on lactogenic hormones, growth factors, and cell-cell and cell-substrate interactions, all of which modulate transcription factors essential for milk protein gene expression. The CCAAT/enhancer binding protein (C/EBP) family and the signal transducer and activator of transcription 5 (Stat5) have been implicated in mammary epithelial cell growth and differentiation. We have investigated the effects of extracellular matrix components and lactogenic hormones on C/EBP and Stat5 activity. In the mammary gland, tenascin is expressed mainly during embryogenesis and carcinogenesis and in cell culture tenascin downregulates beta-casein gene expression. In HC11 mammary cells, we found that tenascin, but not laminin or fibronectin, specifically downregulated C/EBPalpha levels but had no effect on Stat5 amount or DNA binding activity. Furthermore, we found that the lactogenic hormones, glucocorticoids, prolactin, and insulin, had no effect on C/EBPalpha and C/EBPbeta protein levels but downregulated the DNA binding activity of the transcriptional repressor C/EBPbetaLIP. Thus, C/EBPalpha and beta are regulated by tenascin and lactogenic hormones in mammary epithelial cells.

Animals↗
PubMed2000

The expression of teneurin-4 in the avian embryo.

The teneurins are a family of four transmembrane proteins expressed in the developing vertebrate nervous system, though the Drosophila teneurin ten-m is also a pair-rule gene. Whole-mount in situ hybridization was used to localize teneurin-4 transcripts in the chicken embryo. The earliest signal is detected at stage 19 in the somites and limb buds. By stage 20 teneurin-4 transcripts are detected in temporal periocular mesenchyme, branchial arches, diencephalon and somites. Teneurin-4 expression in the limbs changes dramatically during development. Between stages 19 and 21 teneurin-4 expression is concentrated proximally in the zone of polarizing activity. Between stages 24 and 26 teneurin-4 is expressed in the mesenchyme of the anterodistal part of the limb. As in Drosophila, vertebrate teneurins are expressed not only in the nervous system, but also in non-neuronal tissues during pattern formation.

Amino Acid Sequence↗
PubMed1999

Tenascin-Y, a component of distinctive connective tissues, supports muscle cell growth.

Chicken tenascin-Y is an extracellular matrix protein most closely related to the mammalian tenascin-X. It is highly expressed in the connective tissue of skeletal muscle (C. Hagios, M. Koch, J. Spring, M. Chiquet, and R. Chiquet-Ehrismann, 1996, J. Cell Biol. 134, 1499-1512). Here we demonstrate the presence of tenascin-Y in specific areas of the connective tissues in developing lung, kidney, and skin. In skin tenascin-Y shows a complementary expression pattern to tenascin-C, whereas in the lung and kidney the sites of expression are partly overlapping. Tenascin-Y is also present in embryonic skeletal muscle where it is expressed in the developing connective tissue in between the muscle fibers. This connective tissue is also the major site of alpha5 integrin expression. We purified recombinantly expressed tenascin-Y and tested its effect on cell adhesion and its influence on muscle cell growth and differentiation. C2C12 myoblasts were able to adhere to tenascin-Y and showed extensive formation of actin-rich processes without generation of stress fibers. Furthermore, we found that tenascin-Y influenced cell morphology of chick embryo fibroblasts over prolonged times in culture and that it supports primary muscle cell growth and restricts muscle cell differentiation.

Animals↗
PubMed1999

Teneurins: a novel family of neuronal cell surface proteins in vertebrates, homologous to the Drosophila pair-rule gene product Ten-m.

We have characterized chicken teneurin-1 and teneurin-2, two homologues of the Drosophila pair-rule gene product Ten-m and Drosophila Ten-a. The high degree of conservation between the vertebrate and invertebrate proteins suggests that these belong to a novel family. We propose to name the vertebrate members of this family teneurins, because of their predominant expression in the nervous system. The expression of teneurin-1 and -2 was investigated by in situ hybridization. We show that teneurin-1 and -2 are expressed by distinct populations of neurons during the time of axonal growth. The most prominent site of expression of chicken teneurins is the developing visual system. Recombinant teneurin-2 was expressed to assay its molecular and functional properties. We show that it is a type II transmembrane protein, which can be released from the cell surface by proteolytic cleavage at a furin site. The expression of teneurin-2 in neuronal cells led to a significant increase in the number of filopodia and to the formation of enlarged growth cones. The expression pattern of teneurins in the developing nervous system and the ability of teneurin-2 to reorganize the cellular morphology indicate that these proteins may have an important function in the formation of neuronal connections.

Amino Acid Sequence↗
PubMed1999

Mouse ten-m/Odz is a new family of dimeric type II transmembrane proteins expressed in many tissues.

The Drosophila gene ten-m/odz is the only pair rule gene identified to date which is not a transcription factor. In an attempt to analyze the structure and the function of ten-m/odz in mouse, we isolated four murine ten-m cDNAs which code for proteins of 2,700-2, 800 amino acids. All four proteins (Ten-m1-4) lack signal peptides at the NH2 terminus, but contain a short hydrophobic domain characteristic of transmembrane proteins, 300-400 amino acids after the NH2 terminus. About 200 amino acids COOH-terminal to this hydrophobic region are eight consecutive EGF-like domains. Cell transfection, biochemical, and electronmicroscopic studies suggest that Ten-m1 is a dimeric type II transmembrane protein. Expression of fusion proteins composed of the NH2-terminal and hydrophobic domain of ten-m1 attached to the alkaline phosphatase reporter gene resulted in membrane-associated staining of the alkaline phosphatase. Electronmicroscopic and electrophoretic analysis of a secreted form of the extracellular domain of Ten-m1 showed that Ten-m1 is a disulfide-linked dimer and that the dimerization is mediated by EGF-like modules 2 and 5 which contain an odd number of cysteines. Northern blot and immunohistochemical analyses revealed widespread expression of mouse ten-m genes, with most prominent expression in brain. All four ten-m genes can be expressed in variously spliced mRNA isoforms. The extracellular domain of Ten-m1 fused to an alkaline phosphatase reporter bound to specific regions in many tissues which were partially overlapping with the Ten-m1 immunostaining. Far Western assays and electronmicroscopy demonstrated that Ten-m1 can bind to itself.

Alkaline Phosphatase↗
PubMed1999

wing blister, a new Drosophila laminin alpha chain required for cell adhesion and migration during embryonic and imaginal development.

We report the molecular and functional characterization of a new alpha chain of laminin in Drosophila. The new laminin chain appears to be the Drosophila counterpart of both vertebrate alpha2 (also called merosin) and alpha1 chains, with a slightly higher degree of homology to alpha2, suggesting that this chain is an ancestral version of both alpha1 and alpha2 chains. During embryogenesis, the protein is associated with basement membranes of the digestive system and muscle attachment sites, and during larval stage it is found in a specific pattern in wing and eye discs. The gene is assigned to a locus called wing blister (wb), which is essential for embryonic viability. Embryonic phenotypes include twisted germbands and fewer pericardial cells, resulting in gaps in the presumptive heart and tracheal trunks, and myotubes detached from their target muscle attachment sites. Most phenotypes are in common with those observed in Drosophila laminin alpha3, 5 mutant embryos and many are in common with those observed in integrin mutations. Adult phenotypes show blisters in the wings in viable allelic combinations, similar to phenotypes observed in integrin genes. Mutation analysis in the eye demonstrates a function in rhabdomere organization. In summary, this new laminin alpha chain is essential for embryonic viability and is involved in processes requiring cell migration and cell adhesion.

Alleles↗