ARTICLE |
Correspondence to: Donald Gullberg, Dept. of Cell & Molecular Biology, Uppsala University, BMC Box 596, S-751 24 Uppsala, Sweden. E-mail: Donald.Gullberg@zoofys.uu.se (preferred for correspondence).
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Summary |
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In addition to being the specialized site for transmission of force from the muscle to the tendon, the myotendinous junction (MTJ) also plays an important role in muscle splitting during morphogenesis. An early event in the formation of the MTJ is a regional deposition of basement membranes. We used immunocytochemistry to investigate the distribution of laminin chains during the development of MTJs in human limb muscle at 822 weeks of gestation (wg) and in adult MTJs. We used polyclonal antibodies and a new monoclonal antibody (MAb) against the human laminin 1 G4/G5 domains. At 810 wg, laminin
1 and laminin
5 chains were specifically localized to the MTJ. Laminin
1 chain remained restricted to the MTJ at 22 wg as the laminin ß2 chain had appeared, whereas the laminin
5 chain became deposited along the entire length of the myotubes from 12 wg. In the adult MTJ, only vestigial amounts of laminin
1 and laminin
5 chains could be detected. On the basis of co-distribution data, we speculate that laminin
1 chain in the forming MTJ undergoes an isoform switch from laminin 1 to laminin 3. Our data indicate a potentially important role for laminin
1 chain in skeletal muscle formation. (J Histochem Cytochem 48:201209, 2000)
Key Words:
myotendinous junction, laminin 1 chain, development, human, muscle
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Introduction |
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Muscle development is a complex process characterized by well-regulated expression of a large number of genes, with the corresponding accumulation of specific proteins in intricate temporal and spatial patterns (-chain, a ß-chain, and a
-chain. To date, five different laminin
-chains,
1
5, three ß-chains, ß1ß3, and three
-chains,
1
3, have been characterized and form distinct isoforms, laminins 112 (
7ß1 integrin (
2 chain (
7ß1 integrin (
7-chain in mice selectively affects myotendinous junctions (
In this study we investigated the distribution of different laminin chains in the forming and mature human MTJ. Our data indicate that initially both laminin 1 and laminin
5 chains appear to be selectively deposited at the MTJ in the absence of the laminin ß2 chain. The laminin
1 chain remains restricted to this subdomain of the muscle basement membrane as the laminin ß2 chain appears at the MTJ, whereas the laminin
5 chain becomes deposited along the entire basement membrane with time. The localized expression of laminin
1 chain at the MTJ is developmentally regulated, and further maturation occurs later in development or postnatally because this laminin chain was present only in vestigial amounts in the adult MTJ. Our data point to important roles for laminin
1 in MTJ formation and also indicate that during a developmental window the rare laminin-3 isoform might be present at the MTJ.
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Materials and Methods |
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Muscle Samples
A total of 14 limb muscle samples were obtained from 10 human fetuses legally aborted at approximately 8, 9, 10, 14, 18, 20, and 22 weeks of gestation (wg). Four normal muscle biopsies and two muscle samples obtained post mortem were used to study the adult MTJ. In addition, sections from two muscle biopsies from patients who were diagnosed with Duchenne muscular dystrophy, were also used to further ascertain the specificity of the monoclonal antibody (MAb) against the laminin 1 chain. The muscle samples were collected with the approval of the Ethical Committee of the Medical Faculty, Umeå University and in accordance with the Declaration of Helsinki of 1975. The muscle samples were rapidly frozen in propane chilled in liquid nitrogen and stored at -80C until use. Serial cross-sections (5 µm thick) were cut in a ReichertJung cryostat and stored at -30C until processing for immunohistochemistry.
Western Blotting
In a pilot study, the polyclonal antibodies hLN-1G4/G5 to human laminin
1 revealed discrete but very restricted staining at MTJ in human fetal muscle. To confirm the validity of this staining, we tested the reactivity of these antibodies by Western blotting. Human fetal leg muscle of 11 wg was snap-frozen. The tissue was thawed and laminins were extracted for 2 hr on ice after sonication of the tissue in 10 mM Tris-HCl, pH 7.4, 0.15 M NaCl, and 10 mM EDTA containing protease inhibitors. After centrifugation for 20 min at 11,000 x g, extracted proteins were subjected to electrophoresis under reducing conditions on 5% SDS-PAGE. As a control, human laminin-1 purified from conditioned JAR cell media (Champliaud and Gullberg, unpublished data) was run in a parallell lane. Electrophoretically separated proteins were transferred to nitrocellulose, incubated with antibodies to hLN-
1G4/G5 specific for the 400-kD laminin
1 chain and the blot was developed using the ECL system (Amersham; Poole, UK) as described (
1 chain was expected to be very low. This was also observed when the immunoblot was developed. Whereas a strong laminin
1 chain signal appeared in the control lane, a band at the laminin
1 chain position in the muscle extract was seen only after prolonged exposures (not shown).
Immunohistochemistry
The sections were processed for immunohistochemistry with the following previously characterized antibodies: MAb 4C12 against laminin ß1/1 chain (Immunotech, Marseille, France; diluted 1:1000); MAb 1928 against laminin ß1 chain (Chemicon, Temecula, CA; diluted 1:500); MAb C4 to laminin ß2 chain (
1G4/G5 against the 400-kD laminin
1 chain (
2 chain (provided by E. Engvall, La Jolla, CA; diluted 1:250); MAb BM-2 against laminin
3 chain (
5 chain (diluted 1:3000); MAb B8B11 (provided by M.-F. Champliaud, Charlestown, MA; diluted 1:100) against laminin
2 chain; polyclonal antibodies R16 (
3 chain; MAb 143 DB7 against all known isoforms of tenascin-C (
When this study was almost completed, the MAb 163 DE4 was made available. This MAb was generated by immunizing Balb/C mice with a recombinant laminin 1 chain polypeptide corresponding to the G4/G5 region of human laminin
1. We used this MAb (diluted 1:100) to confirm the data obtained with the polyclonal antibody to the laminin
1 chain.
The tissue sections were air-dried for 1530 min, rehydrated in PBS for 5 min, and then incubated with 5% normal rabbit serum (Dako; Copenhagen, Denmark) for 15 min to inhibit unspecific staining. The sections were then incubated overnight with the appropriate primary antibody at 4C. The primary antibodies were diluted in PBS with 0.1% bovine serum albumin. Thereafter, the sections were washed in PBS and again incubated with normal rabbit serum for 15 min, followed by incubation with rabbit anti-mouse IgG (Dako) for 30 min at room temperature. After washing in PBS for 15 min, the sections were incubated with peroxidasemouse anti-peroxidase complex (Dako) for 30 min and then washed in PBS for 15 min. Normal swine serum, swine anti-rabbit IgG, and peroxidaserabbit anti-peroxidase complex were used on the sections treated with the polyclonal antibodies. Development of peroxidase was obtained by applying a solution containing 1 mg/ml of diaminobenzidine and H2O2 for 510 min, followed by rinsing in running water for 5 min. Finally, the sections were dehydrated in graded concentrations of ethanol followed by xylene and mounted with DPX.
Additional sections were processed using the Vectastain Elite ABC peroxidase system (Vector Laboratories; Burlingame, CA).
Double labelings were obtained with indirect immunofluorescence technique by sequential incubations with two primary antibodies raised in different species and using secondary antibodies conjugated to either red Cy3 (for rat MAb 1928; Jackson Immuno Research Laboratories; Avondale, PA) or to red or green Alexa fluorochromes (Molecular Probes; Eugene, OR).
Control sections were treated in the same way as described above, except that the incubation with the primary antibody was omitted. Additional control sections were treated with preimmune serum from the rabbit producing the polyclonal antibodies hLN-1G4/G5 to evaluate the level of unspecific staining. The sections were examined and photographed in a Zeiss microscope equipped with epifluorescence, using a CCD camera (DageMTI; Michigan City, MI).
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Results |
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Fetal Muscle
The antibodies against tenascin-C (Figure 1A and Figure 2B) strongly labeled the tendons at all ages, and moderate staining was also observed between individual myotubes and clusters of myotubes at 8 and 10 wg. The myotubes were labeled by the MAb against slow myosin heavy chain (Figure 1B) as previously reported (1 chains. This MAb strongly delineated the contours of the developing myotubes and clusters from 8 wg (Figure 1C), and there was no difference in staining intensity towards the MTJ.
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Polyclonal antibodies against the laminin 1 chain specifically labeled the extracellular matrix at the MTJ in fetal limb muscle from 8 to 22 wg (Figure 1D and Figure 2A2F). These antibodies did not specifically label the myotubes for the remainder of their length. In sections treated with rabbit preimmune serum (Figure 1E), no corresponding staining was observed at the MTJ.
The MAb 163D4 against the laminin 1 chain (Figure 1F) likewise strongly stained the extracellular matrix at the MTJ at all fetal ages and did not stain the contours of the myotubes outside of the MTJ.
Staining with MAb 5H2 against the laminin 2 chain at 810 wg was weak and rather uneven (not shown). At later stages, the staining intensity increased and there was variation among different regions and muscles. The contours of the developing myotubes and the MTJ stained moderately to strongly from 12 wg (Figure 1G).
The MAb BM-2 against the laminin 3 chain did not label developing muscle at any fetal age (not shown).
The MAb 4C7 against the laminin 5 chain labeled the extracellular matrix at the MTJ weakly to moderately at 8 and 10 wg (not shown). This MAb did not stain the contours of the developing myotubes outside the MTJ at 8 wg. From 10 wg, the MAb 4C7 weakly stained the contours of the developing myotubes in some of the muscles. From 12 wg, 4C7 labeled the contours of the myotube clusters and individual myotubes in all limb muscles investigated (Figure 1H). Variation in staining intensity was observed among different muscles and among muscle fascicles after 12 wg, but there was no difference in staining intensity towards the MTJ. Larger blood vessels were labeled by MAb 4C7 at all ages.
The MAb 1928, which is specific for laminin ß1 chain, stained the contours of the developing myotubes weakly to moderately and the MTJ strongly between 8 and 12 wg (Figure 2C). From 14 wg, this MAb strongly stained both the contours of the myotubes and the MTJs (Figure 2E). Double staining with this MAb and the polyclonal antibodies against the laminin 1 chain showed that these chains were co-localized at the MTJ (Figure 2C and Figure 2E).
The MAb C4 against laminin ß2 chain labeled the contours of the individual myotubes weakly to moderately and strongly labeled MTJs (Figure 2F) and motor endplates (not shown) from 20 wg, as previously reported (1 chains of laminin at the MTJ (Figure 2F).
The antibodies B8B11 against 2 chain and R16 against
3 chain of laminin did not stain the extracellular matrix around myotubes or at the MTJ (not shown).
Adult Muscle
The staining pattern obtained with the polyclonal antibodies against laminin 1 chain (Figure 3A) was difficult to interpret and was not clearly different from the pattern seen in the sections treated with the corresponding preimmune serum (Figure 3B). The extracellular matrix of some of the adult MTJs was weakly stained by the MAbs against the laminin
1 chain (Figure 3C). The laminin
1 MAb did not label the extracellular matrix outside the MTJ. In sections from two patients suffering from Duchenne muscular dystrophy, the MAbs to laminin
1 chain failed to stain sarcolemmal basement membranes (not shown), confirming the results previously obtained with the polyclonal antibodies hLN-
1G4/G5 (
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The adult MTJs were weakly stained by the MAb against the 5 chain (Figure 3D) whereas the MAbs against the laminin
2 (Figure 3E) and ß2 (Figure 3F) chains stained the MTJ strongly, in accordance with published results (
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Discussion |
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The finding that defects in the laminin 2 chain can cause muscular dystrophy (
During development and growth, the MTJ is subjected to dynamic changes. Electron microscopic studies of developing embryonic MTJ in avians indicate that basement membrane deposition is one of the first steps in MTJ formation (-chains, knowledge about laminin isoforms in human muscle has been only fragmentary. We have recently shown that the MAb 4C7, suggested to recognize the laminin
1 chain, recognizes the
5 chain, and that laminin
1 is not prominently present in developing adult or dystrophic human skeletal muscle basement membranes (
1ß2
1) really represents laminin 11(
5ß2
1). This updates the question of whether laminin 3 really exists in muscle.
In this study we have analyzed the laminin 1,
2,
3,
5, ß1, ß2,
1,
2, and
3 chains in the developing MTJ. Laminin
1 chain was detected both with polyclonal antibodies and with a recently developed MAb. The specificity of the polyclonal antibody, which is raised to a recombinant protein encompassing the E3 domain, has been previously shown (
1 G4/G5 protein and human laminin 1.
The presence of a basement membrane at early time points was indicated by the staining observed with antibodies to laminin ß1 and laminin ß1/1 chains around the myotubes. The nature of the
-chain trimerizing with the ß1/
1 chains present in the early basement membranes detected around all myotubes is not known because none of the
-chains investigated were initially present in this pattern. Whether laminin
1 chain coexists with or replaces the early isoform of laminin
-chain at the MTJ remains to be determined.
Although reagents to laminin 1 chain in mouse have been available for some time, several groups have reported the lack of laminin
1 in developing skeletal muscle (
1 chain to the MTJ is most likely the reason for the missed detection of laminin
1 chain in previous reports. However, the presence of laminin
1 in the forming MTJ has been reported in the developing mouse (
It is not known what laminin ß-chains the laminin 1 chain associates with at the developing MTJ. It is expected that the amount of laminin
1 chain in muscle is very low, making biochemical and RNA characterizations very difficult to perform. The weak immunoblotting signal obtained from a muscle extract in the present study indicates that we are close to the limit of detection. Biochemical analysis of the chain composition of laminin
1 containing heterotrimers might be even more difficult. Likewise, in situ hybridization analysis will have to be very sensitive to detect the highly restricted laminin
1 expression. Analysis of transgenic mice having lacZ expressed under the control of the laminin
1 promoter might be the most feasible way to resolve the question of the origin of laminin
1 at the MTJ. On the basis of co-distribution patterns, we speculate that the laminin
1 chain is initially present as laminin 1 (
1ß1
1) but that as the laminin ß2 chains start to accumulate, the laminin
1 chain may also exist at the MTJ in the form of laminin 3 (
1ß2
3). This is an interesting possibility that remains to be demonstrated biochemically. We cannot exclude the possibility that laminin
1 chain might form a heterotrimer with a novel ß-chain. In our studies of laminin
1 chain synthesized in vitro or extracted from placenta, we have indirect data suggesting that laminin
1 chain does indeed associate with a novel ß-chain in addition to its associations with laminin ß1 and ß2 in laminin 1 and laminin 3 (M.-F. Champliaud, personal communication).
The presence of laminin 1 chain in developing human muscle was restricted spatially to the MTJ and to some extent temporally, indicated by the weak or absent staining observed in the adult MTJ. We could not determine the exact time point for the downregulation of the laminin
1 chain from the MTJ owing to the fact that material older then 22 wg was not available. However, the presence of this laminin
-chain exclusively at the MTJ during the period of muscle morphogenesis suggests that it might play an important role in tendon attachment of the developing myotubes and that it might participate in such events as regulation of myotube growth as well as muscle splitting and shaping. Recent data revealed the existence of a subcompartment at the ends of primary myotubes, where selective accumulation of the mRNA for a nuclear protein named MARP (muscle ankyrin repeat protein) occurs as a result of signaling from tendon mesenchyme (
An important question pertains to what cells synthesize the laminin 1 chain accumulating at muscle endpoints. Laminin
1 chain can be synthesized either by muscle cells themselves or by other possibly fibroblast-like cells in the tendon. Evidence for the synthesis of laminins by fibroblasts exists in the literature (
-chains at the muscle endpoints suggests the influence of signals from the adjacent tendon mesenchyme.
Laminin 3 chain was not present in basement membranes of muscle fibers. The distribution of laminin
4 chain has not yet been determined in developing human muscle, but in situ hybridization and immunolocalization studies in mouse have revealed laminin
4 chain in the developing skeletal muscle (
4 chain starts to be deposited on myotubes towards the end of the maturation of the primary myotubes (
4 chain disappears from the extrasynaptic sarcolemmal basement membrane. It is possible that laminin
4 chains are structurally "fitted" to accommodate basement membranes of growing cells. In this regard, it is interesting to note that laminin
4 lacks a short arm, which might influence its ability to homopolymerize and also its ability to interact with other ECM components and cells. Laminin
4 mRNA has been detected previously in human muscle (
-chain in developing human muscle.
The early accumulation of laminin 2 and
5 chains at the MTJ was followed by expression of these isoforms along the entire length of the developing myotubes, suggesting that basement membrane remodeling starts at the endpoints of the developing muscle. The patterns of distribution of laminin
1,
5, and ß2 chains in the basement membrane of developing human myotubes were in agreement with previous reports (
In summary, our data show that laminin 1 and laminin
5 are early basement membrane markers for the forming MTJ. At later points, laminin
5 is expressed around the entire myofiber, whereas laminin
1 remains restricted to the endpoints at times when important morphogenic events occur. Experiments are under way to determine the basis for the laminin
1 localization to the muscle endpoints.
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Acknowledgments |
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Supported by grants from the Swedish Medical Research Council (12x-3934), Gustaf V:s Fond (DG), Bergvalls Stiftelse (DG), and the Medical Faculty of the University of Umeå.
We thank Mona Lindström for excellent technical assistance, Eva Engvall and Marie-France Champliaud for providing antibodies, and Peter Ekblom for support and stimulating discussions.
Received for publication April 28, 1999; accepted September 15, 1999.
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Literature Cited |
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![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Aumailley M, Smyth N (1998) The role of laminins in basement membrane function. J Anat 193:1-21[Medline]
Baumeister A, Arber S, Caroni P (1997) Accumulation of muscle ankyrin repeat protein transcript reveals local activation of primary myotube endcompartments during muscle morphogenesis. J Cell Biol 139:1231-1242
Becker S, Pasca G, Strumpf D, Min L, Volk T (1997) Reciprocal signaling between Drosophila epidermal muscle attachment cells and their corresponding muscles. Development 124:2615-2622
Benjamin M, Ralphs JR (1997) Tendon and ligamentsan overview. Histol Histopathol 12:1135-1144[Medline]
Campbell KP (1995) Three muscular dystrophies: loss of cytoskeleton-extracellular matrix linkage. Cell 80:675-679[Medline]
Chiquet M, Fambrough DM (1984) Chick myotendinous antigen. I. A monoclonal antibody as a marker for tendon and muscle morphogenesis. J Cell Biol 98:1926-1936[Abstract]
Durbeej M, Henry MD, Campbell KP (1998) Dystroglycan in development and disease. Curr Opin Cell Biol 10:594-601[Medline]
Duxon MJ, Usson Y (1989) Cellular insertion of primary and secondary myotubes in embryonic rat muscles. Development 107:243-251[Abstract]
Ekblom M, Klein G, Mugrauer G, Fecker L, Deutzmann R, Timpl R, Ekblom P (1990) Transiently and locally restricted expression of laminin A chain mRNA by developing epithelial cells during kidney organogenesis. Cell 60:337-346[Medline]
Engvall E, Earwicker D, Haaparanta T, Ruoslahti E, Sanes JR (1990) Distribution and isolation of four laminin variants: tissue restricted distribution of heterotrimers assembled from five different subunits. Cell Regul 1:731-740[Medline]
Gullberg D, Tiger CF, Velling T (1999) Laminins during muscle development and in muscular dystrophies. Cell Mol Life Sci 56:442-460[Medline]
Gullberg D, Velling T, Lohikangas L, Tiger CF (1998) Integrins during muscle development and in muscular dystrophies. Front Biosci 9:1028-1039
Gullberg D, Velling T, Sjöberg G, Salmivirta K, Gaggero B, Edström L, Sejersen T (1997) Tenascin-C expression correlates to macrophage invasion in Duchenne muscular dystrophy and in myositis. Neuromusc Disord 7:39-54[Medline]
Hauschka SD (1994) The embryonic origin of muscle. In Engel AG, FranziniArmstrong C, eds. Myology. 2nd ed New York, McGraw Hill, 3-73
Hayashi YK, Chou F-L, Engvall E, Ogawa M, Matsuda C, Hirabayashi S, Yokochi K, Ziober BL, Kramer RH, Kaufman SJ, Ozawa E, Goto Y, Nonaka I, Tsukahara T, Wang J-Z, Hoffman EP, Arahata K (1998) Mutations in the integrin 7 gene cause congenital myopathy. Nature Genet 19:94-97[Medline]
HelblingLeclerc A, Zhang X, Topaloglu H, Cruaud C, Tesson F, Weissenbach J, Tome FM, Schwartz K, Fardeau M, Tryggvason K, Guicheny P (1995) Mutations in the laminin alpha 2-chain gene (LAMA2) cause merosin-deficient congenital muscular dystrophy. Nature Genet 11:216-218[Medline]
Hillaire D, Leclerc A, Faure S, Topaloglu H, Chiannilkulchai N, Guicheney P, Grinas L, Legos P, Philpot J, Evangelista T, Routon MC, Mayer M, Pellissier JF, Estournet B, Barois A, Hentati F, Feingold N, Beckmann JS, Dubowitz V, Tome FMS, Fardeau M (1994) Localization of merosin-negative congenital muscular dystrophy to chromosome 6q2 by homozygosity mapping. Hum Mol Genet 3:1657-1661[Abstract]
Hughes S, Cho M, KarschMizrachi I, Travis M, Silberstein L, Leinwand LA, Blau HM (1993) Three slow myosin heavy chains sequentially expressed in developing mammalian skeletal muscle. Dev Biol 158:183-199[Medline]
Hunter DD, Shah V, Merlie JP, Sanes JR (1989) A laminin-like adhesive protein concentrated in the synaptic cleft of the neuromuscular junction. Nature 338:229-234[Medline]
Iivanainen A, Kortesmaa J, Sahlberg C, Morita T, Bergmann U, Thesleff I, Tryggvason K (1997) Primary structure, developmental expression, and immunolocalization of the murine laminin 4 chain. J Biol Chem 272:27862-27868
Jobsis GJ, Keizers H, Vreijling JP, de Visser M, Speer MC, Wolterman RA, Baas F, Bolhuis PA (1996) Type VI collagen mutations in Bethlehem myopathy, an autosomal dominant myopathy with contractures. Nature Genet 14:113-115[Medline]
Koch M, Olson PF, Albus A, Jin W, Hunter DD, Brunken WJ, Burgeson RE, Champliaud MF (1999) Characterization and expression of the laminin 3 chain: a novel, non-basement membrane-associated, laminin chain. J Cell Biol 145:605-618
Kühl U, Öcalan M, Timpl R, Mayne R, Hay E, von der Mark K (1984) Role of muscle fibroblasts in the deposition of type IV collagen in the basal lamina of myotubes. Differentiation 28:164-172[Medline]
Mayer U, Saher G, Fassler R, Bornemann A, Echtermeyer F, von der Mark H, Miosge N, Poschl E, von der Mark K (1997) Absence of integrin alpha 7 causes a novel form of muscular dystrophy. Nature Genet 17:318-323[Medline]
Monical PL, Kefalides NA (1994) Coculture modulate laminin synthesis and mRNA levels in epidermal keratinocytes and dermal fibroblasts. Exp Cell Res 210:154-159[Medline]
Patton BL, Miner JH, Chiu AY, Sanes JR (1997) Distribution and function of laminins in the neuromuscular system of developing, adult, and mutant mice. J Cell Biol 139:1507-1521
Richards A, Al-Imara L, Pope FM (1996) The complete cDNA sequence of laminin 4 and its relationship to the other human laminin
chains. Eur J Biochem 238:813-821[Abstract]
Rousselle P, Lunstrum GP, Keene DR, Burgeson RE (1991) Kalinin: an epithelium-specific basement membrane adhesion molecule that is a component of anchoring filaments. J Cell Biol 114:567-576[Abstract]
Sanderson RD, Fitch JM, Linsenmayer TR, Mayne R (1986) Fibroblasts promote the formation of a continous basal lamina during myogenesis in vitro. J Cell Biol 102:740-747[Abstract]
Schuler F, Sorokin L (1995) Expression of laminin isoforms in mouse myogenic cells in vitro and in vivo. J Cell Sci 108:3795-3805
Senga K, Kobayashi M, Hattori H, Yasue K, Mizutani H, Ueda M, Hoshino T (1995) Type VI collagen in mouse masseter tendon, from osseous attachment to myotendinous junction. Anat Rec 243:294-302[Medline]
Song WK, Wang W, Foster RF, Bielser DA, Kaufman SJ (1992) H36-7 is a novel integrin alpha chain that is developmentally regulated during skeletal myogenesis. J Cell Biol 117:643-657[Abstract]
Tidball JG, Lin C (1989) Structural changes at the myogenic cell surface during the formation of the myotendinous junction. Cell Tissue Res 257:77-84[Medline]
Tiger CF, Champliaud MF, PedrosaDomellöf F, Thornell LE, Gullberg D (1997) Presence of laminin alpha5 chain and lack of laminin alpha1 chain during human muscle development and in muscular dystrophies. J Biol Chem 272:28590-28595
Tiitta O, Wahlström T, Paavonen J, Linnala A, Sharma S, Gould VE, Virtanen I (1992) Enhanced tenascin expression in cervical and vulvar koilocytic lesions. Am J Pathol 141:907-913[Abstract]
Timpl R (1996) Macromolecular organization of basement membranes. Curr Opin Cell Biol 8:618-624[Medline]
Wewer UM, Thornell LE, Loechel F, Zhang X, Durkin ME, Amano S, Burgeson RE, Engvall E, Albrechtsen R, Virtanen I (1997) Extrasynaptic location of laminin beta 2 chain in developing and adult human skeletal muscle. Am J Pathol 151:621-631[Abstract]
Xu H, Christmas P, Wu XR, Wewer UM, Engvall E (1994a) Defective muscle basement membrane and lack of M-laminin in the dystrophic dy/dy mouse. Proc Natl Acad Sci USA 91:5572-5576[Abstract]
Xu H, Wu XR, Wewer UM, Engvall E (1994b) Murine muscular dystrophy caused by a mutation in the laminin alpha 2 (Lama2) gene. Nature Genet 8:297-302[Medline]