Electric-induced reversal of morphogenesis in Hydra regeneration

Morphogenesis in whole-body regeneration requires the dynamic interplay of three types of processes: biochemical, mechanical and electrical, which span all scales from the molecular to the entire organism. Despite significant progress in elucidating the role of these processes in morphogenesis, understanding their integration into a robust body-plan remains elusive. Here we employ external electric fields and study their effect on morphogenesis during Hydra regeneration. We show the existence of a critical electric field at which the process of morphogenesis halts. Remarkably, above this critical field morphogenesis exhibits reversal dynamics; a fully developed animal flows back into its incipient spheroid morphology, which nevertheless can regenerate again when the amplitude of the external electric field is reduced below criticality. This controlled backward-forward cycle of morphogenesis can be repeated several times. The folding back of morphology is accompanied by the gradual decay of the Wnt3 activity, a central component of the head organizer in Hydra, which re-emerges upon renewed regeneration. We further show that electric-induced reversal of morphogenesis is triggered by enhanced electrical activity of the Hydra tissue. The external field stimulates an increase in the epithelium spike-like calcium activity, which in turn is demonstrated to follow electrical spike bursts. The existence of a ~1 kHz upper frequency cutoff of the external AC field and the emergence of similar behavior at an elevated external potassium (K+) concentration, strengthen the conclusion that enhanced electrical excitability is the underlying mechanism of morphogenesis reversal. Controlled reversal trajectories open a new vista on morphogenesis and suggest a novel approach to study regeneration as well as potential applications in regenerative medicine.