The Regenerative Stage‐Defined Neurogenic Properties in the Spinal Cord of <i>Xenopus laevis</i> : Correlation Between Neurogenic Potential and Functional Repair of the Spinal Cord

Many treatments for spinal cord injury (SCI) have been developed; however, none of these treatments enable complete functional repair. In this study, we utilized a model amphibian, Xenopus laevis, which has regeneration capacity of the spinal cord in the tadpole stages but loses it during metamorphosis, to identify differences in spinal cord properties between the regenerative and non-regenerative stages. We compared the spatiotemporal expression patterns of transcription factors important for neural tube development as well as cell proliferation markers between tadpoles and metamorphosed young adults (froglets) in Xenopus as well as between Xenopus and mouse embryos. We found that Xenopus drastically changed properties in ependymal cells of the spinal cord during the transition from regenerative to non-regenerative stages, and that similar change occurred in the mouse neural tube between 12.5 and 14.5 dpc, during which neurogenesis is known to cease. We then investigated neurogenic activity during Xenopus metamorphosis by labeling newly generated neurons and found that it was correlated with regeneration capacity. We also found that neurogenesis actively occurred after SCI at the regenerative stages but was scarcely reactivated at the non-regenerative stages, suggesting that neurogenesis may play an important role in the process of spontaneous regeneration in Xenopus. We propose that supplying neurons as a treatment for SCI is a valid strategy based on principles of regeneration, which are naturally possessed by regenerative animals.