THE ability of cells to interact and communicate is a biological phenomenon that developed with the evolution of multicellular organisms. The cell-cell interactions that have evolved are essential for the survival of both simple organisms such as dictyostelium and complex organisms such as mammals. These cellular associations allow an organism to develop capacities that are greater than the simple sum of their individual parts. As early as 1878, Claude Bernard proposed that the “milieu interieur” (i.e. internally produced fluid environment) and a cybernetic-like control system (i.e. cell-cell interactions and communication) in multicellular organisms are needed to adaptively regulate the growth, development, and maintenance of normal tissue function (1, 2). The experimental analysis of cellular interactions was initiated with the investigation of cell aggregation in simple organisms such as sponges (3, 4) and progressed into the areas of embryology (5) and cell biology (6, 7). Analysis of cell biology on a molecular level has revealed the importance of cell-cell interactions during embryo-genesis, organogenesis, and determination of cell lineage (reviews in Refs. 8–12).