Summary of the signals, pathways and cellular behavior of Nematostella wound healing. (A) Potential tissue interactions that initiate the transition from wound healing to regeneration. Puncture wound healing involves collapsing of tissue due to the compromised tissue walls, resulting in cells becoming compacted in local proximity to the wound. Tissue like the mesenteries could provide local signals to aid in initiating wound healing as it comes in contact with the injury site in both puncture assays and decapitated animals. Wound healing-related gene expression is found locally around the site of injury and along the mesenteries during healing. Apoptosis is a known regulator of future proliferation during regeneration and is active during Nematostella wound healing. (B) Timeline of events leading to a regenerative response. Wound healing and regeneration in Nematostella appear to be developmentally separable processes, where wound healing initiates regeneration. Apoptosis is activated immediately after injury, where proliferation may be the key transition for a regenerative response. MAPK-ERK signaling spans over the whole regenerative process, potentially regulating cellular movement and/or recognition during wound healing and proliferation during regeneration. We did not find any evidence that Notch signaling effects the wound healing process, but rather inhibited head regeneration. The Wnt planar cell polarity pathway is likely to effect wound healing and is known to regulate axis formation during regeneration.