Integrins and extracellular matrix in animal models

Integrins are a family of transmembrane receptors that mediate interactions of cells with extracellular matrix (ECM) constituents and cell surface counter receptors. Each integrin mediates interactions with specific sets of ligands and regulates distinct aspects of cellular function including attachment to and organization of ECM assemblies, cell migration, proliferation and survival, and mechanical force transmission. Integrins exert their versatile functions by establishing a transmembrane link between the cell exterior and the cytoskeleton, and by activating intracellular second messenger systems. In addition, cellular signals can modulate integrin activity and ligand interactions, enabling transduction of information from the inside of the cell to the outside. Many of the basic functions of integrins and their ECM ligands have been uncovered by studying them biochemically or with cells in culture. Integrin and ECM functions have also been determined genetically, defining their essential roles in the organism. The ongoing challenge is to integrate cell biological, biochemical, and genetical evidence into a coherent picture. I will discuss here genetic findings, focusing on the murine system, that have shed light on the developmental functions of integrins and their ECM ligands. Where suitable information is available, I will relate the genetical finding to results obtained with cell biological and biochemical approaches.