Long Range Communication via Gap Junctions and Stress in Planarian Morphogenesis: A Computational Study

Abstract

Developmental morphogenesis reliably builds species-specific large-scale anatomies. Crucially, regulative development and regeneration after diverse and unpredictable damage illustrate that groups of cells deploy context-sensitive, homeostatic algorithms that can navigate anatomical state space in flexible ways. While the molecular machinery necessary for this process is increasingly becoming characterized, the algorithms that guide growth and form are still poorly understood. To drive progress in regenerative medicine and bioengineering, constructive models need to be formulated and tested that show the kinds of information exchange sufficient for specific morphogenetic competencies. Here, we propose a computational model of planarian regeneration that relies on cell-cell communication via gap junction channels and the use of stress as a driver of homeostatic change. We simulate key experiments in the planarian model system and show that this framework is sufficient to demonstrate the observed regenerative behavior of planaria under bioelectric perturbation. This model suggests testable hypotheses in vivo, and it provides a framework for design strategies for control circuits in synthetic bioengineering.