Contact interactions between epitheliocytes and fibroblasts: Formation of heterotypic cadherin-containing adhesion sites is accompanied by local cytoskeletal reorganization

Contact interactions between different cell types play a number of importan t roles in development, for example in cell sorting, tissue organization; a nd ordered migration of cells. The nature of such heterocellular interactio ns, in contrast to interactions between cells of the same type, remains lar gely unknown. In this report, we present experimental data examining the dy namics of heterocellular interactions between epitheliocytes and fibroblast s, which express different cadherin cell adhesion molecules and possess dif ferent actin cytoskeletal organizations. Our analysis revealed two striking features of heterocellular contact. First, the active free edge of an epit heliocyte reorganizes its actin cytoskeleton after making contact with a fi broblast. Upon contact with the leading edge of a fibroblast, epitheliocyte s disassemble their marginal bundle of actin filaments and reassemble actin filaments into a geometric organization more typical of a fibroblast lamel la. Second, epitheliocytes and fibroblasts form cell-cell adhesion structur es that have an irregular organization and are associated with components o f cell adhesion complexes. The structural organization of these adhesions i s more closely related to the type of contacts formed between fibroblasts r ather than to those between epitheliocytes. Heterotypic epithelio-fibroblas tic contacts, like homotypic contacts between fibroblasts, are transient an d do not lead to formation of stable contact interactions. We suggest that heterocellular contact interactions in culture may be regarded as models of how tissue systems consisting of epithelia and mesenchyme interact and bec ome organized in vivo.