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Cover   This electron micrograph illustrates the tripartite nature of the junctions that lie at the apex between two intestinal epithelial cells (Farquhar, M.G., and Palade, G.E. Junctional Complexes in Various Epithelia, J. Cell Biol. 17, 375-412, 1963). The micrograph is part of a study that included many tissues from both rats and guinea pigs: intestine (as shown here), stomach, gall bladder, uterus, oviduct, liver, pancreas, parotid, thyroid, and kidney. The organization shown, which is known as a "junctional complex," is representative of many of the epithelia studied, though variations were described. Characteristic of the time and of these authors, the paper is admirably thorough, including 30 figures to provide complete documentation of the points made.  The uppermost part of the junctional complex was christened by the authors the "zonula occludens," (occluding belt) or tight junction. In the preparation shown, the outer surfaces of the opposing membranes in this region appear to be fused, suggesting a barrier to diffusion of molecules from the lumen that lies at the apex of the epithelium to the basolateral extracellular space. This inference was verified in the paper cited by the demonstration that extracellular hemoglobin is unable to penetrate the tight junction, suggesting that it serves the role of an intercellular "seal."  Below the zonula occludens are the zonula adherens, or adhering belt, and the macula adherens, or spot desmosome. These structures were interpreted as parts of the mechanism by which adjacent epithelial cells attach to one another, forming a mechanically stable sheet. Although the subsequent work of Farquhar and Palade did not focus on junctional complexes, this initial description clearly implied that the molecular components of the various elements of this complex would differ. More recently many scientists have participated in identifying these molecules: occludin, ZO1, ZO2, and cingulin are specific to the zonula occludens; E-cadherin, the catenins, and actin filaments are concentrated in the zonula adherens; and desmosomes contain other cadherins (the desmogleins and desmocollins) and intermediate filaments.J.R. McIntosh and K.E. Howell