MEAT SCIENCE AND MUSCLE BIOLOGY SYMPOSIUM: Extracellular matrix regulation of skeletal muscle formation 1,2 S. G. Velleman 3 Department of Animal Sciences, Ohio Agricultural Research and Development Center, The Ohio State University, Wooster 44691 ABSTRACT: Skeletal muscle development and growth is a complex process that involves the interac- tion of muscle cells with their extracellular environment. Because muscle development involves the interaction of the cell surface and extracellular matrix molecules, research focus has been placed on the proteoglycans. Proteoglycans are macromolecules containing a central core protein with attached carbohydrates, called gly- cosaminoglycans, that are located at both the cell sur- face and the extracellular matrix. Research focus has been placed on understanding the mechanisms of the membrane-associated heparan sulfate proteoglycans, syndecan-4 and glypican-1, which are both capable of regulating cellular responsiveness to fibroblast growth factor 2 (FGF2). Fibroblast growth factor 2 is a po- tent stimulator of muscle cell proliferation and a strong inhibitor of differentiation. Studies on syndecan-4 and glypican-1 show that these proteoglycans differentially regulate muscle cell proliferation, differentiation, and cellular responsiveness to FGF2 with syndecan-4 pre- dominantly modulating muscle cell proliferation and glypican-1 modulating differentiation. Site-directed mutagenesis approaches were used to define the effect of the syndecan-4 and glypican-1 covalently attached side chains on their activity. In general, a functional association was found between the glycosaminoglycan and N-glycosylated chains attached to the central core proteins of syndecan-4 and glypican-1 affecting their regulation of muscle cell proliferation, differentiation, and FGF2 responsiveness. Current research efforts are directed at identifying the cellular signaling pathways modulated by syndecan-4 and glypican-1. Key words: extracellular matrix, glypican-1, muscle, proteoglycan, satellite cell, syndecan-4 ©2012 American Society of Animal Science. All rights reserved. J. Anim. Sci. 2012. 90:936–941 http://dx.doi.org/10.2527/jas.2011-4497 INTRODUCTION Skeletal muscle growth and development are highly organized processes regulated by interactions between muscle cells and their extracellular environment. Dur- ing early embryonic development, muscle cells are de- rived from mesodermal precursor cells originating from mesodermal somites (Asakura et al., 2002). Muscle precursor cells become committed myoblasts, then dif- ferentiate into myocytes, and eventually fuse to form multinucleated myofibers (for review, see Chargé and Rudnicki, 2004). These changes in the state of muscle cells are due to cell adhesion, cell migration, and cell- to-cell interactions, which are regulated by signals from the extracellular environment. Communication between the extracellular matrix (ECM) and muscle cells has a pivotal role in the regu- lation of muscle cell proliferation and differentiation. Proliferation represents the replication of muscle cells available to fuse and differentiate into multinucleated myotubes, whereas differentiation refers to the develop- ment of muscle-specific structures including multinucle- ated myotubes and fibers. Increased proliferation will provide a larger pool of muscle cells available for dif- ferentiation. Changes in the level of differentiation will affect muscle fiber size and the number of muscle fibers. The ECM is a dynamic network of molecules secreted by the cells and includes collagens, proteoglycans, and noncollagenous glycoproteins. Traditionally, the ECM was described as a ground substance that the cells were embedded in and functioned as a structural framework 1 Based on a presentation at the Meat Science and Muscle Biology Symposium, “Extracellular matrix in skeletal muscle development and meat quality,” at the Joint Annual Meeting, July 10 to 14, 2011, New Orleans, Louisiana, with publication sponsored by the Ameri- can Society of Animal Science and the Journal of Animal Science. 2 Salary and partial research support to S. G. Velleman were pro- vided by state and federal funds appropriated to the Ohio Agricul- tural Research and Development Center, The Ohio State University (Wooster), the Midwest Poultry Research Consortium (Minneapolis, MN), and the National Research Initiative Competitive Grant No. 2009-35503-05176 from the USDA National Institute of Food and Agriculture (Washington, DC). 3 Corresponding author: Velleman.1@osu.edu Received July 21, 2011. Accepted August 27, 2011. 936 Published January 20, 2015