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PubMed1999

Tenascin-Y in the developing and adult avian nervous system.

The glycoproteins tenascin-C and tenascin-R are abundant in the developing and adult nervous system, respectively. We have used a polyclonal antiserum to determine if tenascin-Y, a novel member of the tenascin family previously identified in the extracellular matrix of muscle, is also expressed in the avian nervous system. Beginning at embryonic day 3 tenascin-Y immunoreactivity is associated with bottle-shaped ependymal cells in the roof plate and floor plate of the spinal cord and brain. These cells resemble the secretory cells that synthesize the ventricular extracellular matrix, including Reissner's fiber. Tenascin-Y immunoreactivity is also seen in pia mater and blood vessels in the developing and adult central nervous system. Anti-tenascin-Y stains the connective tissue sheath of peripheral nerves and the dorsal roots beginning around embryonic day 20. In vitro, sensory neurites fail to form lamellipodia when cultured in the presence of recombinant tenascin-Y, suggesting that tenascin-Y may play a role in inhibiting sensory neurite regeneration into the spinal cord. There is little overlap in the expression patterns of tenascin-Y and tenascin-C during development and between tenascin-Y and tenascin-R in the adult central nervous system, which is further evidence of distinctive mechanisms of gene regulation by the different members of the tenascin family.

Animals↗
PubMed1996

Modulation of osteoblast behaviour by tenascin.

The extracellular matrix protein tenascin is secreted by osteoblasts but absent from mineralized bone matrix. The current study was undertaken to test the hypothesis that tenascin regulates osteoblast behaviour. Three osteoblast-like cell lines UMR-106, ROS-17/2.8 (rat) and SAOS-2 (human) were used to investigate the role of tenascin in osteoblast morphology, differentiation and proliferation. Two of three cell lines adhered specifically to tenascin, remaining round and failing to spread. Tenascin as a substratum stimulated alkaline phosphatase activity (a marker of osteoblast differentiation) in two of three cell lines. Moreover, anti-tenascin in the medium caused a reduction in alkaline phosphatase levels in all three cell lines. Anti-tenascin also inhibited collagen synthesis, an important osteoblast function. Since it seemed possible that tenascin may exert its effects on cell function through its ability to cause cell rounding, the ability of cell shape change alone to influence alkaline phosphatase levels was investigated. Cells were incubated in the presence of cytochalasin D and alkaline phosphatase levels assayed. Alkaline phosphatase activity was not elevated by cytochalasin D treatment, indicating that cell rounding alone is insufficient to mimic the effect of tenascin. Anti-tenascin caused a slight increase in proliferation of SAOS-2 cells, indicating that tenascin is itself inhibitory. In ROS 17/2.8 and UMR-106 cells, in contrast, proliferation was inhibited by anti-tenascin. The results presented here indicate that tenascin is able to stimulate osteoblastic differentiation and that endogenous tenascin helps to maintain the functional state of cultured osteoblast-like cells.

Alkaline Phosphatase↗
PubMed1994

Tenascin-contactin/F11 interactions: a clue for a developmental role?

To understand how the extracellular matrix glycoprotein tenascin modifies cell adhesion and neurite outgrowth, we sought to isolate cellular receptors for tenascin. So far, two completely different cell surface ligands for tenascin have been detected. This we achieved by affinity chromatography of tissue extracts and of isolated proteins over tenascin-Sepharose and by solid-phase assays using the individual proteins. The first receptor, the neuronal cell adhesion molecule contactin/F11, a member of the immunoglobulin superfamily, binds to tenascin via a site in the N-terminal immunoglobulin-like domains. The binding site is within the fibronectin type III homology region at the boundary of the alternatively spliced region of tenascin, requiring that fibronectin type III homology domains 5 and 9 be adjacent, as they are in the 190 kD tenascin isoform. The close similarity in tertiary structure between type III domains and immunoglobulin-like repeats raises the possibility that we are observing a side-by-side interaction between the two molecules in a manner closely analogous to that between paired immunoglobulin domains. The second receptor is the heparan sulfate proteoglycan, glypican, which, similarly to contactin/F11, is anchored to the membrane via glycosylphosphatidylinositol. Glypican bound to a column of tenascin-Sepharose cannot be dissociated by chondroitin sulfate or dermatan sulfate, but elutes in a broad peak with a gradient of heparan sulfate and in a sharper peak with heparin. By means of fusion proteins, we have identified a potential binding site on the fifth fibronectin type III homology domain of tenascin. We are trying to define these sites more closely by means of site-directed mutagenesis. It will be interesting to see whether the interaction between tenascin and cell surface contactin/F11, and possibly cellular heparan sulfate proteoglycans, contributes to the prominent role played by tenascin in pattern formation during development of the nervous system. In a first step, we have examined the distribution of tenascin isoforms and contactin/F11 during retinal development by means of immunohistochemistry and in situ hybridization with tenascin isoform-specific probes. Tenascin isoforms 190/200 along with contactin/F11 are particularly prominent in the inner and outer plexiform layers of embryonic day 8 retina in the chick. This coordinate up-regulation was confirmed both by immunoblots and Northern blots of retinal extracts. A speculative model is presented to suggest how the unique hexabrachion may signal the cell via contactin/F11.

Amino Acid Sequence↗
PubMed1999

Tenascin-C in the cochlea of the developing mouse.

Tenascin-C is a glycoprotein of the extracellular matrix that acts in vitro as both a permissive and a nonpermissive substrate for neurite growth. We analyzed, by immunocytochemistry, the distribution of tenascin-C along neural growth pathways in the developing mouse cochlea. In the spiral lamina, tenascin-C coexists in a region where nerve bundles arborize. In the organ of Corti, tenascin-C lines the neural pathways along pillar and Deiters' cells before and during the time of nerve fiber ingrowth. By embryonic day 16, tenascin-C is abundant on the pillar side of the inner hair cell but does not accumulate on the modiolar side until about birth, a time after the arrival of afferent fibers. The synaptic zones beneath outer hair cells are strongly labeled during the time when early events in afferent synaptogenesis are progressing but not during the time of efferent synaptogenesis. At the age when most neural growth ceases, tenascin-C immunoreactivity disappears. Faint tenascin-C immunolabeling of normal hair cells, strong tenascin immunolabeling in pathological hair cells of Bronx waltzer (bv/bv) mice, and staining for beta-galactosidase, whose gene replaces tenascin in a "knockout" mouse, indicate that hair cells supply at least part of the tenascin-C. The changing composition of the extracellular matrix in the synaptic region during afferent and efferent synaptogenesis is consistent with a role for tenascin in synaptogenesis. The presence of tenascin-C along the growth routes of nerve fibers, particularly toward the outer hair cells, raises the possibility that growth cone interactions with tenascin-C helps to guide nerve fibers in the cochlea.

Aging↗
PubMed1995

The expression, origin and function of tenascin during peripheral nerve formation in the chick.

During development of the peripheral nervous system, the extracellular matrix molecule tenascin has been found to be closely associated with growing axons. However, its origin and function in peripheral nerve formation are far from clear. In this study, we examined the expression of tenascin during outgrowth of sensory, motor and sympathetic preganglionic axons, and assessed its origin and function in peripheral nerve formation. During outgrowth of sensory and motor axons, a high concentration of tenascin and its mRNA was found to surround sensory and motor axons in the newly formed spinal nerves. The source of this tenascin was examined through a series of surgical manipulations. Neural crest removals did not alter the distribution of tenascin protein or its mRNA surrounding the spinal nerves. Transplantation of quail somites into chick embryos showed that, similar to the distribution of tenascin, there is a high concentration of somitic cells surrounding the spinal nerves. Moreover, somite removals resulted in a reduction of the tenascin and tenascin mRNA surrounding the spinal nerves. Taken together, these results suggest that the majority of the tenascin surrounding the spinal nerves is of somitic origin. Possible functions of tenascin associated with peripheral nerve formation were examined through injections of tenascin or its antiserum into individual somites prior to or during axon outgrowth. Injections of tenascin or its antiserum did not alter the trajectory of peripheral axons in the anterior half of the somite, nor produce gross abnormalities in the morphology of peripheral nerves, suggesting that tenascin does not play a crucial role in the early formation of peripheral nerves.

Animals↗
PubMed2004

Tenascins.

Tenascins are a family of large multimeric extracellular matrix (ECM) proteins. Vertebrates express four tenascins termed tenascin-C, -R, -X and -W present in their connective tissues. Each tenascin has a specific expression pattern. To the contrary of many other ECM proteins, tenascins promote only weak cell adhesion and do not activate cell spreading. They have been classified as anti-adhesive, adhesion-modulating or even repellent ECM proteins. Tenascin-C and tenascin-R deficient mice show abnormalities in the nervous system and tenascin-C deficient mice, in addition, have defects in several regenerative processes. Mice lacking tenascin-X display hyperelastic skin much like Ehlers Danlos patients with mutations in their tenascin-X gene. Since tenascin-C is highly overexpressed in tumor stroma antibodies against tenascin-C have been used in tumor diagnosis and therapy. Since tenascins are known to influence cell shape, migration and growth they represent good candidate molecules for inclusion in artificial bioengineered tissue implants.

Animals↗
PubMed1994

Tenascin-C expression by fibroblasts is elevated in stressed collagen gels.

Chick embryo fibroblasts cultured on a collagen matrix exert tractional forces leading to the contraction of unrestrained, floating collagen gels and to the development of tension in attached, restrained gels. On a restrained, attached collagen gel the fibroblasts synthesize large quantities of tenascin-C, whereas in a floating, contracting gel tenascin-C synthesis is decreased. This regulation of tenascin-C synthesis can be observed by the secretion of metabolically labeled tenascin-C into the conditioned medium, as well as by the deposition of tenascin-C into the collagen matrix as judged by immunofluorescence. Regulation appears to occur at the transcriptional level, because when cells on attached or floating collagen gels are transfected with promoter constructs of the tenascin-C gene, luciferase expression driven by the tenascin-C promoter parallels the effects measured for endogenous tenascin-C synthesis, whereas luciferase expression under the control of the SV40 promoter does not depend on the state of the collagen gel. The promoter region responsible for tenascin-C induction on attached collagen gels is distinct from the region important for the induction of tenascin-C by serum, and may define a novel kind of response element. By joining this tenascin-C sequence to the SV40 promoter of a reporter plasmid, its activity can be transferred to the heterologous promoter. We propose that the tenascin-C promoter is directly or indirectly activated in fibroblasts generating and experiencing mechanical stress within a restrained collagen matrix. This may be an important aspect of the regulation of tenascin-C expression during embryogenesis as well as during wound healing and other regenerative and morphogenetic processes.

Animals↗
PubMed1997

Human epidermal keratinocytes are a source of tenascin-C during wound healing.

Tenascin-C is a large hexameric extracellular matrix glycoprotein that is expressed in a temporally and spatially restricted pattern associated with stromal-epithelial interactions. In adult human skin, the expression level of tenascin-C is low, but tenascin-C is abundantly present in the dermal compartment during embryogenesis and wound healing and in skin tumors. Herein we have investigated the cellular source of tenascin-C production in human skin, both in vivo and in vitro, by using immunohistochemistry, mRNA in situ hybridization, western blotting, and an enzyme-linked immunosorbent assay. In addition we studied the cell-matrix interaction between epidermal keratinocytes and purified tenascin-C. By using in vitro culture models, we found that keratinocytes not only synthesize and secrete tenascin-C but can also deposit tenascin-C in de-epidermized dermis in a pattern that is very similar to that in vivo. In vivo, during wound healing of normal human skin, we found tenascin-C extracellularly in the wound bed and also in a granular pattern within the neo-epidermis. By mRNA in situ hybridization, we could identify the basal migrated keratinocytes as the main source of tenascin-C in the early phase of wound healing. In the granulation phase, tenascin-C expression by the keratinocytes is downregulated. Cultured keratinocytes were found to adhere poorly to tenascin-C, and those that did adhere retained a rounded morphology. We conclude that human keratinocytes are a major source of tenascin-C during the early phase of wound healing, and we hypothesize that tenascin-C is unlikely to be an adhesive substrate for migrating keratinocytes.

Cell Adhesion↗
PubMedDate not supplied

Functional aspects of vascular tenascin-C expression.

The arterial tenascin C expression in vivo and in vitro has been studied using immunohistochemistry. The functional relevance of localized tenascin C expression was assessed in vitro using various human cell types involved in the progression of vascular disease. Normotensive and hypertensive rats exhibited age-dependent patterns of vascular (aorta) tenascin expression, but the lumen-to-media-directed progression of tenascin induction was accelerated in hypertensive rats. Tenascin-rich neointimal lesions (spontaneous) were observed at branching sites of aorta from aged (80 weeks) hypertensive rats. Subendothelial tenascin foci contained lipid-laden smooth muscle cells and monocytes/macrophages. Medial tenascin foci encaged smooth muscle cells which synthesized DNA. Tenascin was expressed both in vivo and in vitro by endothelial and smooth muscle cells but not by monocytes/macrophages; angiotensin II, oxidized-low density lipoprotein and transforming growth factor beta 1 induced expression of tenascin transcripts and glycoprotein in vitro. Endothelial and smooth muscle cells, but not monocytes, adhered to tenascin substrata. Tenascin reduced focal adhesion integrity in confluent endothelial and smooth muscle cell cultures. Angiotensin II-induced migration of endothelial and smooth muscle cells was accompanied by tenascin deposition within extracellular matrix migration trails. Tenascin may function both as a defense against monocyte invasion and medial smooth muscle replication, as well as a substratum for directed endothelial and smooth muscle cell migration.

Animals↗
PubMed1993

Dual function of tenascin: simultaneous promotion of neurite growth and inhibition of glial migration.

The extracellular matrix molecule tenascin is expressed within the developing peripheral nervous system, first by migrating neural crest cells and later by satellite (Schwann precursor) cells at the growing tips of peripheral nerves. Here we found that the neurite promoting activity of tenascin for sensory neurons is developmentally regulated: very young sensory ganglia of stage 23 (4 days old) embryos grew neurites on tenascin as fast as on laminin and fibronectin. The growth response of older (day 7 and 9) ganglia on laminin and fibronectin was similar to that of 4-day-old ganglia, while on tenascin neurite growth occurred only after a lag phase and at a slower rate. Neurite growth on tenascin was inhibited by antibodies to beta 1 integrin and by heparin. While tenascin promotes neurite outgrowth of peripheral neurons, we found that it does not allow satellite cell migration when it is present on the substratum, and it inhibits migration of satellite cells on fibronectin when added in soluble form. In contrast, soluble tenascin did not significantly alter the rate of neurite growth on tenascin, fibronectin or laminin substrata, although neurites were straighter and less attached. When isolated satellite cells were added to neurites grown on tenascin, they preferentially adhered to and elongated along neurite surfaces. Using patterned substrata of tenascin versus fibronectin or laminin confirmed that tenascin borders allow neurites to pass but act as barriers to migrating satellite cells. We postulate that tenascin or related molecules with dual functions in cell adhesion are important for peripheral nerve morphogenesis. Tenascin allows axonal growth, but may restrict random satellite cell migration into the fibronectin-rich mesenchyme, thereby inducing the compaction of nerve fascicles.

Animals↗
PubMed1995

Mammary epithelial cell differentiation in vitro is regulated by an interplay of EGF action and tenascin-C downregulation.

Expression of the extracellular matrix glycoprotein tenascin-C in the mammary gland is associated with cellular proliferation and cell motility during organogenesis and tumorigenesis. Because the source and the regulation of tenascin-C in these tissues are unclear, we have used tenascin-C cDNA, FITC-immunofluorescence and immuno-precipitation to examine tenascin-C expression of mammary epithelial cells. Using several mammary epithelial cell lines we could show that tenascin-C can be produced and secreted by epithelial cells. However it was found that tenascin-C synthesis was inversely correlated with the polarized epithelial phenotype. Among three mouse mammary epithelial cell clones, tenascin-C expression was most abundant in HC-11 cells, the least differentiated cell type. Expression levels were high during the growth phase but were nearly abolished when cells were grown to confluence and induced to express milk proteins. Downregulation of tenascin-C by EGF apparently commits HC-11 cells to respond to lactogenic hormones and consequently, hormone induced levels of beta-casein mRNA decreased significantly when HC-11 cells were grown on a tenascin-C substrate. On the other hand, TGF-beta, another growth factor involved in coordinated growth and differentiation of the mammary gland in vivo was found to be a very potent inducer of tenascin-C. The generation of fully polarized and tight epithelium affected the levels of tenascin-C expression. In contrast to HC-11 cells, which do not form epithelial domes in vitro, highly polarized and dome forming EpH4 and Fos-ER cells nearly lacked tenascin-C. Similarly, induction of dome formation in the rat mammary stem cell line Rama 25 by the differentiation inducer dimethylsulfoxide caused a loss of TN-C-transcripts. The inability of Fos-ER cells to develop domes in the presence of soluble tenascin-C also suggests its interference with induction and maintenance of mammary epithelial cell differentiation.

Animals↗
PubMed1992

Expression of tenascin in the developing and adult cerebellar cortex.

Since tenascin may influence neuronal cell development, we studied its expression pattern using immunocytochemistry, in situ hybridization, Northern blot analysis, and immunochemistry in the developing and adult mouse cerebellar cortex. Tenascin immunoreactivity was detectable in all layers of the developing cerebellar cortex. In the external granular layer, only the radially oriented processes of Golgi epithelial cells were immunoreactive, whereas the densely packed cell bodies were immunonegative. Tenascin was hardly detectable at contact sites between migrating granule cells and processes of Golgi epithelial cells. Axons of granule cells in the molecular layer were immunoreactive, whereas their cell bodies in the internal granular layer lacked detectable levels of tenascin. By in situ hybridization, only Golgi epithelial cells and astrocytes of the internal granular layer and prospective white matter, but not nerve cells, could be shown to synthesize detectable levels of tenascin mRNA in the developing mouse cerebellar cortex. Thus, tenascin in the cerebellar cortex seems to be a glia-derived molecule that becomes adsorbed to neuronal surfaces in a topographically restricted pattern in situ. Levels of tenascin protein and mRNA decreased significantly with increasing age. In the adult, tenascin immunoreactivity was weak and mainly restricted to the molecular layer and tenascin mRNA was confined to Golgi epithelial cells, indicative for a functional heterogeneity in differentiated cerebellar astrocytes. Quantitative immunoblot analysis revealed that the 225 and 240 kDa components of tenascin were developmentally downregulated at a faster rate than the 190 and 200 kDa components, corresponding to the faster downregulation of the 8 kilobase (kb) mRNA species compared to the 6 kb mRNA species as revealed by Northern blot analysis. These observations indicate a differentially regulated expression of the tenascin components. We hypothesize that glia-derived tenascin modifies the functional properties of nerve cell surfaces and that tenascin is involved in such different morphogenetic events as neurite growth and oligodendrocyte distribution.

Animals↗
PubMed2003

[Tenascin-C expression in human breast tumors].

INTRODUCTION: Increased amounts of extracellular matrix proteins have been described in breast tumours, which are normally present in embryonal connective tissue, in adults however, these occur only in pathological conditions: one of which is tenascin. Within the tenascin family the most examined and most controversial member is tenascin-C. It has been suggested that tenascin-C decreases cell adhesion, promotes invasion and metastases, and may play role in pathological angiogenesis. MATERIAL AND METHODS: Authors investigated 62 primary breast carcinomas and in further 20 cases both the primary and the recurrent or second primary tumours were examined. In the latter group the main question was whether tenascin-C was of prognostic significance. The newly formed vessels were visualised using CD31 antibody. RESULTS AND CONCLUSIONS: Tenascin-C positivity in the tumour cells was shown in the 10 of the 62 primary carcinomas and in 7 from the second group of cases (20 patients). Of all cases examined, in five specimens tenascin-C positivity was present in normal ductal epithelial cells. In variable amount, in the stroma of invasive tumours, tenascin-C was present in every case. The presence of tenascin-C within tumour cells, at the periphery and also in the stroma of tumours, within the proliferating ducts, around tumour cell nests and in situ carcinomas, furthermore, in the epithelial cells of normal ducts suggests that tenascin-C may promote detachment and migration of carcinoma cells. There was no correlation, however, between tenascin-C expression and the occurrence of recurrences in this small group. Correlation was found between increased stromal tenascin-C expression and angiogenesis. Authors conclude that tenascin-C might have a role in angiogenesis.

Adult↗
PubMed1988

Immunocytochemical localisation of tenascin during the development of scleral papillae and scleral ossicles in the embryonic chick.

We have used a polyclonal antibody against tenascin (a 240 kDa extracellular matrix glycoprotein) and indirect immunofluorescence to investigate the distribution of tenascin in cryostat sections of the chick sclera during the six stages of scleral papilla development (Murray, 1943) and formation of membrane bone anlagen (mesenchymal condensations between 6-12 days of incubation - HH Stage 29-37). At Stages 1 and 2, when the papilla was a slight thickening in the conjunctival epithelium and mesenchymal condensation formation was initiated, tenascin was sparse in the sclera. At Stage 3, when the papilla had an epithelial mass intruding into the mesenchyme, there was an accumulation of tenascin fibrils along the subsurface of the papilla with fibrils extending from this region into the mesenchymal condensation. Interestingly, tenascin was sparse between papillae and between mesenchymal condensations. The Stage 4 papilla had a similar localisation of tenascin fibrils and in addition fine arborizing fibrils of tenascin were observed within the basal epithelia of the papilla adjacent to the epithelial-mesenchymal interface (which suggested that the fibrils infiltrated through the basement membrane region). The Stage 5 and 6 papillae had a column of vertical tenascin fibrils extending from the subsurface of the papilla to the interior mesenchyme corresponding exactly to the location of the mesenchymal condensation which was then forming the anlage of the ossicle in a flat bed about 100 microns from the conjunctival surface. The column of tenascin disappeared as the osteoid appeared in the ossicular bed on the 12th day of incubation but a dense accumulation of tenascin remained along the subsurface of the papilla. With the exception of tenascin fluorescence in the basal region of the Stage 4 papilla, tenascin fibrils were not observed in the other stages of papilla development in the epithelium covering areas between the mesenchymal condensation. This restricted distribution of tenascin may be important in the morphogenesis of scleral papillae and scleral ossicles.

Animals↗
PubMed1993

Tenascin function and regulation of expression.

Tenascin is a large hexameric extracellular matrix protein. Each subunit consists of a linear array of the following structural domains: an N-terminal cysteine-rich region and heptad repeats both involved in the oligomerization, followed by EGF-like repeats, fibronectin type III domains and a C-terminal globular domain homologous to fibrinogens. Depending on the species, the number of EGF-like repeats as well as of the fibronectin type III repeats differs. A model proposing a new nomenclature for the numbering of the fibronectin type III repeats is presented. It enables the assignment of corresponding repeats from different species and shows that for human tenascin several more alternatively spliced fibronectin type III repeats have been described than for chicken or mouse tenascin. Tenascin is generally classified as an anti-adhesive protein, since many cells do not adhere to tenascin or if they adhere they do not spread. The addition of tenascin can also lead to the loss of focal contacts in well spread cells. On the other hand growth cones adhere well to tenascin and a tenascin substrate can support neurite extension. Using recombinant fragments of tenascin we could identify an adhesive as well as an anti-adhesive region within one tenascin subunit. The major interest in tenascin was prompted by its interesting tissue distribution. Tenascin is often transiently expressed during organogenesis, tissue remodeling, cell migration and the development of the nervous system. We thus investigated possibilities to regulate tenascin expression in primary chick embryo fibroblast cultures.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Tenascin protein and mRNA in the avian visual system: distribution and potential contribution to retinotectal development.

The large glycoprotein tenascin is one of the extracellular matrix proteins that is abundant in the developing nervous system. To determine its distribution and possible role in the ontogenty of the avian retinotectal system, the distribution of the protein, the expression of its mRNA, and the effect of the protein on growing retinal neurites in vitro was investigated. Immunocytochemistry demonstrated that relatively little tenascin was present in the optic fiber layer of the retina, the optic nerve and tract. Tenascin, however, was abundant in the stratum opticum of the tectum, the target of retinal axons in the brain. Whereas tenascin protein is found only in discrete portions and layers of the brain, in situ hybridization studies showed that tenascin mRNA was expressed throughout development by radial glial cells at the ventricular surfaces of the brain, distant from the tissue localization of the protein. Injection of antitenascin antiserum into the tectal ventricle disturbed the distribution of the protein in the tectum by binding tenascin closer to its origin at the ventricular border. This suggests that the localization of tenascin in the brain is not restricted to its site of synthesis, but is mediated by tenascin-binding proteins that are expressed in defined areas and layers in the brain. In vitro studies showed that tenascin did not promote neurite outgrowth of retinal axons. On the contrary, the addition of tenascin to retinal explants growing on collagen or on L1 slowed the growth rate of optic axons by as much as 50%. The inhibitory function in vitro suggests that this protein has a modulatory role in axonal growth in vivo. The absence of tenascin from the optic fiber layer of retina, optic nerve, and optic tract and its abundance in the tectum suggest that tenascin may function to slow the rapidly growing optic nerve fibers once they arrive at the tectum. The slowing of optic fiber outgrowth may then facilitate terminal arborization and synapse formation within the tectum. The abundant tenascin in synaptic layers may also serve to stabilize synapses once they have formed.

Animals↗
PubMed1995

Tenascin knockout mice: barrels, boundary molecules, and glial scars.

In light of a previous report suggesting that the brains of tenascin-deficient animals are grossly normal, we have studied the somatosensory cortical barrel field and injured cerebral cortex in postnatal homozygous tenascin knockout, heterozygote, and normal wild-type mice. Nissl staining, cytochrome oxidase, and Dil axonal tracing of thalamocortical axonal projections to the somatosensory cortex, all reveal the formation of normal barrels in the first postnatal week in homozygous knockout mice that cannot be distinguished from heterozygote or normal wild-type barrels. In addition to confirming the absence of tenascin in knockout animals, and reporting apparently reduced levels of the glycoprotein in barrel boundaries of heterozygote animals using well-characterized antibodies and immunocytochemistry, we also studied the DSD-1-PG proteoglycan, another developmentally regulated molecule known to be associated with transient glial/glycoconjugate boundaries that surround developing barrels; DSD-1-PG was also found to be expressed in barrel boundaries in apparently normal time frames in tenascin knockout mice. Peanut agglutinin (PNA) binding of galactosyl-containing glycoconjugates also revealed barrel boundaries in all three genotypes. We also examined the expression of tenascin-R, a paralog of tenascin-C (referred to here simply as tenascin). As previously reported, tenascin-R is prominently expressed in subcortical white matter, and we found it was not expressed in the barrel boundaries in any of the genotypes. Thus, the absence of tenascin does not result in a compensatory expression of tenascin-R in the barrel boundaries. Finally, we studied wounds of the cerebral cortex in the late postnatal mouse. The astroglial scar formed, for the most part, in the same time course and spatial distribution in the wild-type and tenascin knockout mice. However, there may be some differences in the extent of gliosis between the knockout and the wild type that warrant further study. Roles for boundary molecules like tenascin during brain pattern formation and injury are reconsidered in light of these findings on barrel development and cortical lesions in tenascin-deficient mice.

Animals↗
PubMed1997

Characterization of monoclonal antibodies against tenascin-C: no apparent effect on kidney development in vitro.

Tenascin-C is an extracellular matrix glycoprotein found in embryonic mesenchyme. The precise biological function of tenascin-C is unknown, but different parts of the molecule have effects on cell adhesion and other cellular activities. We studied the expression and role of tenascin-C in the embryonic mouse kidney. By Northern blots, no tenascin-C was detectable in uninduced mesenchyme from day 11 embryonic kidneys, but after 24 hours of in vitro culture both major splice variants of tenascin-C were detected. The larger variant was the predominant form. By in situ hybridization tenascin-C mRNA in 13-day old embryonic kidneys was detected in the mesenchyme surrounding newly formed epithelial structures. In 17-day old embryonic kidneys, tenascin-C mRNA was detected in mesenchyme around the forming epithelial structures in the cortex, and expression was also seen in mesenchyme surrounding the capsular epithelium of glomeruli. In newborn kidneys, expression had shifted to the medulla but was still confined to mesenchymal areas. We have characterized 6 new monoclonal antibodies against mouse tenascin-C, which all stain embryonic kidneys from different stages in a pattern consistent with earlier reports and with the mRNA data. The binding sites of the monoclonal antibodies on the tenascin-C molecule were mapped to discrete regions of tenascin-C. These six and five previously described antibodies against tenascin-C were tested in antibody perturbation experiments. Three of these have been shown by in vitro assays to perturb function of other cell types. Despite this, none of them inhibited development of mouse kidneys in organ culture, although they were tested at 1 mg/ml. It raises the possibility that tenascin-C is not crucial for kidney development. Alternatively, tenascin-C has more subtle functions which could not be identified with the assays used here.

Animals↗