[Between homeostasis and development, which strategies to regenerate?]

The Hydra model system is well suited to decipher the mechanisms underlying adult regeneration, specifically those that were robust enough to be maintained across evolution. After mid-gastric bissection head regeneration in Hydra relies on apoptosis-induced compensatory proliferation via the release of Wnt3 by the apoptotic interstitial cells and activation of the β-catenin pathway in the surrounding cycling interstitial cells. As apoptosis-induced compensatory proliferation is also at work in Drosophila regenerating imaginal discs, Xenopus tadpole regenerating their tail and mice regenerating their skin or their liver, this mechanism might represent an evolutionarily-conserved way to launch a regenerative response. However after decapitation, the analysis of the activation of the canonical Wnt pathway in decapitated Hydra showed that apoptosis-induced compensatory proliferation does not take place in this context. Given that the proportion of interstitial stem cells is significantly higher in the middle part than in the upper part of the body column, this suggested that the route taken to regenerate a structure as complex as the head dramatically varies according to the homeostatic status of the tissue at the time of injury. From these observations, we propose a tri-modular model for animal regeneration where the first module or "wound healing module" is followed by a transient module named "inducing module of regeneration" that allows the recruitment of the third module named "re-development module", necessary for repatterning the missing structure. We claim that among these three modules, the inducing module of regeneration is the most drastically constrained by the homeostatic conditions of any given tissue or organ at the time of injury and therefore the most variable.