Self vs nonself in tissue assembly: Correlated changes in recognition behavior and tissue cohesiveness

Vertebrate embryonic cell populations of unlike kind, when combined in vitro, typically spread around and sort out from one another in combination-specific patterns, whereas like cell populations merely coalesce. These differing responses to self and nonself constitute one form of morphogenetic self-recognition behavior. Prolonged shaker-flask culturing and dissociation and reaggregation of embryonic chick heart tissue were both previously shown to reverse the tissue's spreading behavior with liver. Here, we show that these treatments simultaneously initiate, in heart tissue, a “foreign” spreading reaction toward untreated heart. Moreover, the direction of this heart-heart spreading can be deduced from the change in direction of heart-liver spreading. This suggests that certain properties of heart tissue participate in the determination of both the foreign- and the self-recognition behaviors studied here. The differential adhesion hypothesis postulates that these properties are the intensities of tissue cohesion, with less cohesive tissues enveloping more cohesive ones. If so, our observations imply that heart fragments precultured $\text{1}\text{2}$ day should be more cohesive than $\text{1}\text{2}\text{-}\text{day}$ precultured heart reaggregates, but less cohesive than heart fragments precultured $\text{2}\text{1}\text{2}$ days. With our centrifugation assay, in which relative tissue cohesiveness is assessed by the relative roundness of centrifuged aggregates at shape equilibrium, we confirm this prediction.