Cellular Interactions with Extracellular Matrix During Development and in Muscle Disease

Abstract: The formation and maintenance of tissues in multicellular animals are crucially dependent on cellular interactions with the extracellular matrix (ECM). Two different studies on such interactions are presented herein.Studies on expression of laminins in normal and dystrophic skeletal muscle, clarified a much debated issue regarding discrepancies seen for laminin ?1-chain expression between human and mouse tissues. Lack of laminin ?1-chain expression was verified in both mouse and human skeletal muscle. Furthermore, the earlier discrepancies seen for laminin ?1-chain expression was explained by showing that an antibody-reagent, commonly used in human studies, recognised the laminin ?5-chain rather than the laminin ?1-chainThe integrin ?11-chain (forming ?11?1 integrin) is the latest addition to the integrin receptor family, and belongs to the I domain-containing group of integrin ?-chains. Previous studies had shown that ?11?1 is a collagen receptor. In the present study, the in vitro and in vivo functions of the ?11-chain were further characterised. Distribution studies on embryonic human and mouse tissues showed that the ?11-chain was expressed on mesenchymal cells in the developing tendon, perichondrium, intervertebral disc, and cornea. The interactions of ?11?1 integrin with collagen type I and IV were studied in vitro. The ?11?1 bound to these collagens in a manner similar to integrin ?2?1 (with collagen type I being the preferred ligand for ?11?1). Furthermore, ?11?1 was shown to mediate migration on collagen type I coated surfaces, and to mediate contraction of collagen type I gels. The in vivo functions of the ?11-chain were investigated by the generation of integrin ?11-chain null-mice, using gene targeted disruption of the itga11 in embryonic stem cells. Two independent lines of mice lacking ?11 protein were generated. Phenotypic analysis of these mice indicated a role for ?11?1 in the formation of the musculoskeletal system.