A key question in developmental biology and regenerative medicine concerns the physiological mechanisms by which cells coordinate their behaviors toward the construction and repair of complex anatomical structures. Gap junctional communication among cells enables bioelectrical signaling within a network that enables collections of cells to cooperate during morphogenesis. During regeneration in amputated planarian flatworms, cells capable of dividing must migrate to areas where new tissue is needed. Moreover, these cells must stop proliferating when the needed structures are completed. We previously proposed a cell-cell communication mechanism that enables structure discovery and regeneration by cell networks. In this paper, we further develop the mechanism to address two important simplifications of the previous model: cell division was not limited to adult stem cells (as it is in vivo), and adult stem cells did not migrate to injured areas to initiate the regeneration process. Thus, here we limit cell division to a specific cell type (neoblasts) and propose a second message type that guides neoblasts to locations where cell division is needed. Our results show that even after incorporating these two constraints, our cell-cell communication model maintained its regeneration capabilities against a large tissue removal.

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