Oral Regeneration Is the Default Pathway Triggered by Injury in Hydra

In animals capable of whole-body regeneration, a single bisection injury can trigger two different types of regeneration. Currently, it is not well understood how this adaptive response is transcriptionally regulated. We therefore comprehensively characterized transcript abundance and chromatin accessibility during two types of regeneration, oral and aboral regeneration, in the cnidarian Hydra vulgaris. We found that there was an initial generalized response to injury that was not dependent on the type of structure being regenerated. Canonical Wnt signaling, which specifies oral tissue in cnidarians, was activated during this generalized response, likely through the direct upregulation of Wnt ligands by conserved injury-responsive transcription factors. As regeneration progressed, transcription diverged and Wnt signaling became restricted to oral regeneration. We found that TCF, the transcription factor downstream of Wnt signaling, was required for the initiation of oral and aboral-specific transcription, suggesting that the Wnt pathway is important for both types of regeneration. Finally, we found that Wnt signaling was also activated by puncture wounds and that removing pre-existing organizers induced these injuries to undergo ectopic head regeneration. Our work suggests that injuries activate an oral regeneration program, and that other regeneration outcomes are caused by signals from the surrounding tissue. Furthermore, these findings suggest that Wnt signaling may be part of an ancient and conserved metazoan wound response program predating the split of cnidarians and bilaterians.