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Abstract. Collagen XII has a short collagenous tail and a very large, three-armed NC3 domain consisting primarily of fibronectin type III repeats. Differential splicing within this domain gives rise to a large (320 kD) and a small (220 kD) subunit; the large but not the small can carry glycosaminoglycan. To investigate whether collagen XII variants have distinct expression patterns and functions, we generated antibody and cDNA probes specific for the alternatively spliced domain. We report here that the large variant has a more restricted expression in embryonic tissue than the small. For example, whereas the small variant is widespread in the dermis, the large is limited to the base of feather buds. Distinct proportions of mRNA for the two variants were detected depending on the tissue. Monoclonal antibodies allowed us to separate collagen XII variants, and to show that homo-and heterotrimers exist. Collagen XII variants differ in ligand binding. Small subunits interact weakly with heparin via their COOH-terminal domain. Large subunits have additional, stronger heparin-binding site(s) in their NH2-terminal extra domain. In vivo, both large and small collagen XII are associated with interstitial collagen. Here we show biochemically and ultrastructurally that collagen XII can be incorporated into collagen I fibrils when it is present during, but not after, fibril formation. Removal of the collagenous domain of collagen XII reduces its coprecipitation with collagen I. Our results indicate that collagen XII is specifically associated with fibrillar collagen, and that the large variant has binding sites for extracellular ligands not present in the small variant.group of fibril-associated collagens with interrupted triple helices (FACIT; types IX, XII, XIV) 1 has recently been discovered (for review see Mayne and Brewton, 1993;Shaw and Olsen, 1991;Van der Rest et al., 1990). The prototype FACIT is collagen IX, a heterotrimeric molecule with four noncoUagenous (NC1 to NC4) and three triple-helical domains (Col1 to Col3) (Ninomiya and Olsen, 1984). The et2(IX) chain carries chondroitin sulfate on the NC3 domain (McCormick et al., 1987). Collagen IX is covalently bound to the surface of collagen II fibrils in cartilage (Vaughan et al., 1988;Wu et al., 1992). Its function might be to regulate the diameter of collagen II fibrils, and to link them to other collagen fibrils, extraDrs. Koch, Trueb, and Chiquet's present address is M. E.

The architecture of a tissue is defined by the nature and the integrity of its cellular and extracellular compartments, and is based on proper adhesive cell-cell and cell-extracellular matrix interactions. Cadherins and integrins are major adhesion-mediators that assemble epithelial cells together laterally and attach them basally to a subepithelial basement membrane, respectively. Because cell adhesion complexes are linked to the cytoskeleton and to the cellular signalling pathways, they represent checkpoints for regulation of cell shape and gene expression and thus are instructive for cell behaviour and function. This organization allows a reciprocal flow of mechanical and biochemical information between the cell and its microenvironment, and necessitates that cells actively maintain a state of homeostasis within a given tissue context. The loss of the ability of tumour cells to establish correct adhesive interactions with their microenvironment results in disruption of tissue architecture with often fatal consequences for the host organism. This review discusses the role of cell adhesion in the maintenance of tissue structure and analyses how tissue structure regulates epithelial function.