Cells anchor to substrates by binding to extracellular matrix (ECM). In addition to this anchoring function however, cell-ECM binding is a mechanism for cells to sense their surroundings and to communicate and coordinate behaviour amongst themselves. Several ECM molecules and their receptors play essential roles in muscle development and maintenance. Defects in these proteins are responsible for some of the most severe muscle dystrophies at every stage of life from neonates to adults. However, recent studies have also revealed a role of cell-ECM interactions at much earlier stages of development as skeletal muscle forms. Here we review which ECM molecules are present during the early phases of myogenesis, how myogenic cells interact with the ECM that surrounds them and the potential consequences of those interactions. We conclude that cell-ECM interactions play significant roles during all stages of skeletal muscle development in the embryo and suggest that this "extracellular matrix dimension" should be added to our conceptual network of factors contributing to skeletal myogenesis.

Integrins are cellular adhesion receptors that mediate signaling and play key roles in the development of multicellular organisms. However, their role in the cellular events leading to myotome formation is completely unknown. Here, we describe the expression patterns of the ␣1, ␣4, ␣5, ␣6, and ␣7 integrin subunits in the mouse myotome and correlate them with the expression of several differentiation markers. Our results indicate that these integrin subunits may be differentially involved in the various phases of myogenic determination and differentiation. A detailed characterization of the myogenic cell types expressing the ␣4 and ␣6 subunits showed a regionalization of the myotome and dermomyotome based on cell-adhesion properties. We conclude that ␣6␤1 may be an early marker of epaxial myogenic progenitor cells. In contrast, ␣4␤1 is up-regulated in the intercalated myotome after myocyte differentiation. Furthermore, ␣4␤1 is expressed in the hypaxial dermomyotome and is maintained by early hypaxial myogenic progenitor cells colonizing the myotome. Developmental Dynamics 231:402-415, 2004.

We addressed the potential role of cell-laminin interactions during epaxial myotome formation in the mouse embryo. Assembly of the myotomal laminin matrix occurs as epaxial myogenic precursor cells enter the myotome. Most Myf5-positive and myogeninnegative myogenic precursor cells localise near assembled laminin, while myogenin-expressing cells are located either away from this matrix or in areas where it is being assembled. In Myf5 nlacZ/nlacZ (Myf5-null) embryos, laminin, collagen type IV and perlecan are present extracellularly near myogenic precursor cells, but do not form a basement membrane and cells are not contained in the myotomal compartment. Unlike wild-type myogenic precursor cells, Myf5-null cells do not express the ␣6␤1 integrin, a laminin receptor, suggesting that integrin ␣6␤1-laminin interactions are required for myotomal laminin matrix assembly. Blocking ␣6␤1-laminin binding in cultured wild-type mouse embryo explants resulted in dispersion of Myf5-positive cells, a phenotype also seen in Myf5 nlacZ/nlacZ embryos. Furthermore, inhibition of ␣6␤1 resulted in an increase in Myf5 protein and ectopic myogenin expression in dermomyotomal cells, suggesting that ␣6␤1-laminin interactions normally repress myogenesis in the dermomyotome. We conclude that Myf5 is required for maintaining ␣6␤1 expression on myogenic precursor cells, and that ␣6␤1 is necessary for myotomal laminin matrix assembly and cell guidance into the myotome. Engagement of laminin by ␣6␤1 also plays a role in maintaining the undifferentiated state of cells in the dermomyotome prior to their entry into the myotome.