Old questions, new models: unraveling complex organ regeneration with new experimental approaches.

How do some animals like crabs, flatworms and salamanders regenerate entire body parts after a severe injury? Which are the mechanisms and how did that regenerative ability evolve over time? The ability to regenerate complex organs is widespread in the animal kingdom, but fundamental, centuries-old questions remain unanswered. Forward genetics approaches that were so successful in probing embryonic development are lacking in most regenerative models, and candidate gene approaches can be biased and misleading. We summarize recent progress in establishing new genetic tools and approaches to study regeneration and provide a personal perspective on the feasibility and value of establishing such tools, based on our experience with a new experimental model, the crustacean Parhyale hawaiensis.