Integrins and Development

Cell adhesion is essential for the organization of multicellular organisms. Indeed, various types of cell adhesion receptors, including cadherins and integrins, are present in animals ranging from nematodes and insects to vertebrates. In this book, we focus on the integrin family, which is shared among all metazoans, but has expanded considerably with vertebrate evolution. Since the cloning of the first integrin subunit, some twenty years ago, integrin biology has been—and still is—a topic of intense study. Integrin-mediated adhesion is a regulated process that, in turn, regulates the organization of the actin cytoskeleton. Moreover, it has become clear from in vitro analyses that integrin-mediated adhesion can affect virtually all aspects of cellular behavior—including polarity, motility, proliferation, survival, and differentiation. This book aims to provide an extensive overview of the current knowledge about the regulation of developmental processes as well as the maintenance of proper tissue function, by integrin-mediated adhesion. In addition, key aspects of integrin cell biology are discussed. Chapter 1 of this book is meant as an introduction in integrin biology and is followed by a more in-depth discussion of the roles that integrins play in extracellular matrix assembly, in cell migration, and in the regulation of intracellular signaling cascades (Chapters 2-4). Subsequently, Chapters 5 and 6 discuss what has been learned about the role of integrins and associated proteins in animal development from genetic analysis of two invertebrates— the flatworm, C. elegans and the fruit fly, D. melanogaster. The relatively limited number of genes encoding adhesion-related proteins and the relative ease and speed with which genetic experiments can be performed in these animals, have allowed researchers to study the basic principles of integrin biology in vivo. Finally, Chapters 7-14 discuss how integrin-mediated adhesion regulates the development and functionality of the different mammalian organ systems, based to a large extent on (conditional) gene knockout studies in mice and on studies in human patients.