In some vertebrates, a grave injury to the central nervous system (CNS) results in functional restoration, rather than in permanent incapacitation. Understanding how these animals mount a regenerative response by activating resident CNS stem cell populations is of critical importance in regenerative biology. Amphibians are of a particular interest in the field because the regenerative ability is present throughout life in urodele species, but in anuran species it is lost during development. Studying amphibians, who transition from a regenerative to a nonregenerative state, could give insight into the loss of ability to recover from CNS damage in mammals. Here, we highlight the current knowledge of spinal cord regeneration across vertebrates and identify commonalities and differences in spinal cord regeneration between amphibians.
Some species successfully repair retinal injuries in contrast to non-regenerative mammalian retina. We show here that the Mexican axolotl salamander regrows its excised retina even in adulthood. During early regeneration, cell proliferation occurred in the retinal pigment epithelium (RPE). All dividing cells expressed Vimentin, and some also expressed Müller glia and neural progenitor cell marker Glast (Slc1a3), suggesting that regeneration is driven by RPE-derived retinal progenitor cells. Bulk RNA sequencing showed that genes associated with the extracellular matrix and angiogenesis were upregulated in early-to-mid retinal regeneration. The fully regenerated retina re-established nerve projections to the brain and contained all the original retinal cell types, including Müller glia. Regeneration of cellular diversity may be modulated by Notch signaling, as inhibiting Notch signaling in early regeneration promoted production of rod photoreceptors. Our study highlights the axolotl salamander as an advantageous model of adult tetrapod retinal regeneration and provides insights into its mechanisms.SummaryWe demonstrate that adult Mexican axolotl salamanders regenerate retinas after a retinectomy. We also show some cellular and molecular mechanisms that drive axolotl retinal regeneration.
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