Syndecan-3 and syndecan-4 specifically mark skeletal muscle satellite cells and are implicated in satellite cell maintenance and muscle regeneration

Myogenesis in the embryo and the adult mammal consists of a highly organize d and regulated sequence of cellular processes to form or repair muscle tis sue that include cell proliferation, migration, and differentiation. Data f rom cell culture and in vivo experiments implicate both FGFs and HGF as cri tical regulators of these processes. Both factors require heparan sulfate g lycosaminoglycans for signaling from their respective receptors. Since synd ecans, a family of cell-surface transmembrane heparan sulfate proteoglycans (HSPGs) are implicated in FGF signaling and skeletal muscle differentiatio n, we examined the expression of syndecans 1-4 in embryonic, fetal, postnat al, and adult muscle tissue, as well as on primary adult muscle fiber cultu res. We show that syndecan-1, -3, and -4 are expressed in developing skelet al muscle tissue and that syndecan-3 and -4 expression is highly restricted in adult skeletal muscle to cells retaining myogenic capacity. These two H SPGs appear to be expressed exclusively and universally on quiescent adult satellite cells in adult skeletal muscle tissue, suggesting a role for HSPG s in satellite cell maintenance or activation. Once activated, all satellit e cells maintain expression of syndecan-3 and syndecan-4 for at least 96 h, also implicating these HSPGs in muscle regeneration. Inhibition of HSPG su lfation by treatment of intact myofibers with chlorate results in delayed p roliferation and altered MyoD expression, demonstrating that heparan sulfat e is required for proper progression of the early satellite cell myogenic p rogram. These data suggest that, in addition to providing potentially usefu l new markers for satellite cells, syndecan-3 and syndecan-4 may play impor tant regulatory roles in satellite cell maintenance, activation, proliferat ion, and differentiation during skeletal muscle regeneration. (C) 2001 Acad emic Press.