How the Neighborhood Coherence Principle (NCP) Can Give Rise to Tissue Homeostasis: a Cellular Automaton Approach

Gap junctional intercellular communication (GJIC) might provide a key mechanism for tissue homeostasis. Using a three-dimensional cellular automaton, a model was designed to probe the capacity of the particular cell–cell interaction rule known as the neighbourhood coherence principle (NCP) to produce a control mechanism whereby a cell would be told by its neighbors whether or not to enter a division cycle. A numerical experiment using this model showed that a potent feedback control maintaining a local balance between mitoses, cell differentiation, and death emerged from the sequence of cell growth and maturation events. This regulation stemmed from the interplay of the juvenile and the senescent fractions of a tissue. The regulatory loops shows a variable periodicity which depends on the proportion of daughter cells that take the shortcut to re-enter a division cycle immediately. A distinctive tissue patchiness, an intrinsic feature of systems endowed with the NCP interaction rule, constitutes a predictable feature of real cell systems and allows the formulation of empirically testable hypotheses about the role of GJIC in growth regulation.