Insights into Extracellular Matrix Functions from Mutant Mouse Models

Abstract

The extracellular matrix (ECM) has central roles in tissue integrity and remodeling throughout the life span of animals. While collagens are the most abundant structural components of ECM in most tissues, tissue-specific molecular complexity is contributed by ECM glycoproteins. The matricellular glycoproteins are categorized primarily according to functional criteria and represented predominantly by the thrombospondin, tenascin, SPARC/osteonectin, and CCN families. These proteins do not self-assemble into ECM fibrils; nevertheless, they shape ECM properties through interactions with structural ECM proteins, growth factors, and cells. Matricellular proteins also promote cell migration or morphological changes through adhesion-modulating or counter-adhesive actions on cell–ECM adhesions, intracellular signaling, and the actin cytoskeleton. Typically, matricellular proteins are most highly expressed during embryonic development. In adult tissues, expression is more limited unless activated by cues for dynamic tissue remodeling and cell motility, such as occur during inflammatory response and wound repair. Many insights in the complex roles of matricellular proteins have been obtained from studies of gene knockout mice. However, with the exception of chordate-specific tenascins, these are highly conserved proteins that are encoded in many animal phyla. This review will consider the increasing body of research on matricellular proteins in nonmammalian animal models. These models provide better access to the very earliest stages of embryonic development and opportunities to study biological processes such as limb and organ regeneration. In aggregate, this research is expanding concepts of the functions and mechanisms of action of matricellular proteins.