title: Syndecan-3 and syndecan-4 specifically mark skeletal muscle satellite cells and are implicated in satellite cell maintenance and muscle regeneration.
abstract: Myogenesis in the embryo and the adult mammal consists of a highly organized and regulated sequence of cellular processes to form or repair muscle tissue that include cell proliferation, migration, and differentiation. Data from cell culture and in vivo experiments implicate both FGFs and HGF as critical regulators of these processes. Both factors require heparan sulfate glycosaminoglycans for signaling from their respective receptors. Since syndecans, a family of cell-surface transmembrane heparan sulfate proteoglycans (HSPGs) are implicated in FGF signaling and skeletal muscle differentiation, we examined the expression of syndecans 1-4 in embryonic, fetal, postnatal, and adult muscle tissue, as well as on primary adult muscle fiber cultures. We show that syndecan-1, -3, and -4 are expressed in developing skeletal muscle tissue and that syndecan-3 and -4 expression is highly restricted in adult skeletal muscle to cells retaining myogenic capacity. These two HSPGs appear to be expressed exclusively and universally on quiescent adult satellite cells in adult skeletal muscle tissue, suggesting a role for HSPGs in satellite cell maintenance or activation. Once activated, all satellite cells maintain expression of syndecan-3 and syndecan-4 for at least 96 h, also implicating these HSPGs in muscle regeneration. Inhibition of HSPG sulfation by treatment of intact myofibers with chlorate results in delayed proliferation and altered MyoD expression, demonstrating that heparan sulfate is required for proper progression of the early satellite cell myogenic program. These data suggest that, in addition to providing potentially useful new markers for satellite cells, syndecan-3 and syndecan-4 may play important regulatory roles in satellite cell maintenance, activation, proliferation, and differentiation during skeletal muscle regeneration.
authors.affiliation: Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, Colorado 80309, USA.
authors.forename: D D
authors.initials: DD
authors.lastname: Cornelison
authors.forename: M S
authors.initials: MS
authors.lastname: Filla
authors.forename: H M
authors.initials: HM
authors.lastname: Stanley
authors.forename: A C
authors.initials: AC
authors.lastname: Rapraeger
authors.forename: B B
authors.initials: BB
authors.lastname: Olwin
mesh_terms: D000375:Aging / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D015415:Biomarkers / Q000032:analysis; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D002704:Chlorates / Q000494:pharmacology; D004622:Embryo, Mammalian / Q000166:cytology / Q000187:drug effects / Q000196:embryology / Q000378:metabolism; D005552:Forelimb; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D006497:Heparan Sulfate / Q000494:pharmacology; D007797:Laminin / Q000032:analysis; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D024510:Muscle Development / Q000187:drug effects; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000378:metabolism; D018482:Muscle, Skeletal / Q000166:cytology* / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D017570:MyoD Protein / Q000032:analysis; D011509:Proteoglycans / Q000378:metabolism*; D019859:Proto-Oncogene Proteins c-met / Q000032:analysis; D020794:Receptor Protein-Tyrosine Kinases / Q000032:analysis; D051496:Receptor, Fibroblast Growth Factor, Type 1; D017468:Receptors, Fibroblast Growth Factor / Q000032:analysis; D012038:Regeneration / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D053670:Syndecan-3; D053671:Syndecan-4
chemical_list: D015415:Biomarkers; D002704:Chlorates; D006497:Heparan Sulfate; D007797:Laminin; D008562:Membrane Glycoproteins; D017570:MyoD Protein; D011509:Proteoglycans; D019859:Proto-Oncogene Proteins c-met; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1; D017468:Receptors, Fibroblast Growth Factor; D053670:Syndecan-3; D053671:Syndecan-4; C508302:Sdc3 protein, mouse; C508306:Sdc4 protein, mouse; C496349:Fgfr1 protein, mouse