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 a utomaton, a model was designed to probe the capacity of the particular cell-cell interaction rule known as the neighborhood coherence princi ple (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 mai ntaining a local balance between mitoses, cell differentiation, and de ath emerged from the sequence of cell growth and maturation events. Th is regulation stemmed from the interplay of the juvenile and the senes cent fractions of a tissue. The regulatory loops shows a variable peri odicity which depends on the proportion of daughter cells that take th e shortcut to re-enter a division cycle immediately. A distinctive tis sue patchiness, an intrinsic feature of systems endowed with the NCP i nteraction rule, constitutes a predictable feature of real cell system s and allows the formulation of empirically testable hypotheses about the role of GJIC in growth regulation. (C) 1997 Academic Press Limited .