Ectopic head regeneration after nervous system ablation in a sea anemone

Some animals are able to regenerate all missing cell types and large body parts after bisection, a phenomenon called whole-body regeneration. Many of these animals regenerate the correct tissues and structures with remarkable fidelity according to the original polarity of the body, reflecting positional information present in the remaining tissue. Understanding the cellular and molecular basis of this positional information is a central question in regeneration biology. In planarians and acoels, muscle cells have been shown to carry such positional information, but where this information originates and whether this function is conserved in other highly regenerative animals, is not well understood. Here we use the cnidarian Nematostella vectensis to address the role of the nervous system in whole-body regeneration. We generated a transgenic line for conditional ablation of neurons and first showed that Nematostella can repeatedly regenerate its nervous system. Bisection experiments following nervous system ablation showed that all head fragments regenerate a second head instead of a foot, whereas foot fragments correctly regenerate the missing head. We further found that regenerating head fragments of nervous system-ablated animals increase the expression of Wnt signaling genes that in wildtype animals are only upregulated in regenerating foot fragments. These molecular changes and the initiation of ectopic head regeneration precede the re-appearance of neurons, suggesting that the nervous system does not directly control whether a head or foot will be regenerated. Instead, we propose a model in which the nervous system provides positional information to the tissue of the body column, and that this information allows foot regeneration by suppressing a default program for head regeneration.