Whole-body regeneration is widespread in the Metazoa, yet little is known about how underlying molecular mechanisms compare across phyla. Acoels are an enigmatic phylum of invertebrate worms that can be highly informative about many questions in bilaterian evolution, including regeneration. We developed the three-banded panther worm, Hofstenia miamia, as a new acoelomorph model system for molecular studies of regeneration. Hofstenia were readily cultured, with accessible embryos, juveniles, and adults for experimentation. We developed molecular resources and tools for Hofstenia, including a transcriptome and robust systemic RNAi. We report the identification of molecular mechanisms that promote whole-body regeneration in Hofstenia. Wnt signaling controls regeneration of the anterior-posterior axis, and Bmp-Admp signaling controls regeneration of the dorsal-ventral axis. Perturbation of these pathways resulted in regeneration-abnormal phenotypes involving axial feature duplication, such as the regeneration of two heads following Wnt perturbation or the regeneration of ventral cells in place of dorsal ones following bmp or admp RNAi. Hofstenia regenerative mechanisms are strikingly similar to those guiding regeneration in planarians. However, phylogenetic analyses using the Hofstenia transcriptome support an early branching position for acoels among bilaterians, with the last common ancestor of acoels and planarians being the ancestor of the Bilateria. Therefore, these findings identify similar whole-body regeneration mechanisms in animals separated by more than 550 million years of evolution.
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