Cell adhesion: the molecular basis of tissue architecture and morphogenesis.

A variety of cell adhesion mechanisms underlie the way that cells are organized in tissues. Stable cell interactions are needed to maintain the structural integrity of tissues, and dynamic changes in cell adhesion participate in the morphogenesis of developing tissues. Stable interactions actually require active adhesion mechanisms that are very similar to those involved in tissue dynamics. Adhesion mechanisms are highly regulated during tissue morphogenesis and are intimately related to the processes of cell motility and cell migration. In particular, the cadherins and the integrins have been implicated in the control of cell movement. Cadherin mediated cell compaction and cellular rearrangements may be analogous to integrin-mediated cell spreading and motility on the ECM. Regulation of cell adhesion can occur at several levels, including affinity modulation, clustering, and coordinated interactions with the actin cytoskeleton. Structural studies have begun to provide a picture of how the binding properties of adhesion receptors themselves might be regulated. However, regulation of tissue morphogenesis requires complex interactions between the adhesion receptors, the cytoskeleton, and networks of signaling pathways. Signals generated locally by the adhesion receptors themselves are involved in the regulation of cell adhesion. These regulatory pathways are also influenced by extrinsic signals arising from the classic growth factor receptors. Furthermore, signals generated locally be adhesion junctions can interact with classic signal transduction pathways to help control cell growth and differentiation. This coupling between physical adhesion and developmental signaling provides a mechanism to tightly integrate physical aspects of tissue morphogenesis with cell growth and differentiation, a coordination that is essential to achieve the intricate patterns of cells in tissues.