Developmental onset of planarian whole-body regeneration depends on axis reset.

Regenerative abilities vary across species and developmental stages of animal life cycles. Determining mechanisms that promote or limit regeneration in certain life cycle stages may pinpoint the most critical factors for successful regeneration and suggest strategies for reverse-engineering regenerative responses in therapeutic settings. In contrast to many mammalian systems, which typically show a loss of regenerative abilities with age, planarian flatworms remain highly regenerative throughout adulthood. The robust reproductive and regenerative capabilities of the planarian Schmidtea polychroa (S. polychroa) make them an ideal model to determine when and how regeneration competence is established during development. We report that S. polychroa gradually acquires whole-body regenerative abilities during late embryonic and early juvenile stages. Anterior fragments are capable of regenerating missing trunk and tail tissues from stage 6.5 onward. By contrast, the ability of posterior fragments to make new head tissue depends on the developmental stage, tissue composition of the amputated fragment, and axial position of the cut plane. Irradiation-sensitive cells are required, but not sufficient, for the onset of head regeneration ability. We propose that regulation of the main body axis reset, specifically the ability to remake an anterior organizing center, determines when whole-body regeneration competence arises during development. Supporting this hypothesis, knockdown of the canonical Wnt pathway effector Spol-β-catenin-1, a posterior determinant, induces precocious head regeneration under conditions that are normally head regeneration-incompetent. Our results suggest that regeneration competence emerges through interactions between irradiation-sensitive cells, the cellular source of new tissue, and developing adult tissue(s) harboring axial patterning information.