The cellular and molecular analysis of amphibian spinal cord regeneration, and the comparison with mammalian cells

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Neural stem cells reside in the adult central nervous system, yet the mammalian CNS does not undergo large-scale regeneration probably because the environmental cue present during development are not present in the adult. A major challenge is to induce these stem cells to replace damaged CNS. The urodele amphibian such as the axolotl represents a model to address this issue since spinal cord regeneration involving renewed neurogenesis of all neural cell types occurs after tail amputation. The injured urodele tissue produces an embryonic growth zone capable of reforming a perfect tail. Little is known about how the growth zone is established and the signals in the growth zone that induce the neural stem cells to undergo proliferation and patterning. To address these issues we will use high resolution cell lineage tracing to first define the source of the neural stem cells, how they are recruited to the injury site, and their fate. Second, we will use co-culture assays to determine the source and identity of the key signalling cues that direct neural stem cell proliferation and patterning. Finally, we will co-culture axolotl and mammalian CNS tissue to determine whether axolotl tissue stimulates mammalian stem cells and/or whether mammalian CNS tissue blocks the axolotl response.