| Description |
Newts have an amazing ability to regenerate lost structures and injured tissues. After a complete transection injury, which paralyzes the lower half of the animal, the newt spinal cord regenerates in as little as 4 weeks and re-establishes controlled movement. We have developed new methods of visualizing the cellular and molecular events of spinal cord regeneration and have used these to define six stages of axon regeneration. We also find that axon regeneration appears to be enabled, in part, because the lesion environment is permissive. The extracellular matrix is made up of canonically permissive and inhibitory proteins, but it remains loose and is not dense like it is in mammalian lesions. Meningeal cells and glia are most closely associated with regenerating axons and, instead of forming barriers to axon regeneration as they do in mammals, they appear to assist the regenerative process. Amputated limbs are regenerated in about 7 - 10 weeks. After amputation, mature cells de-differentiate and form a proliferating pool of progenitor cells under the amputation plane called the regeneration blastema. The blastema then organizes itself into a new limb. Little is known about what molecular factors drive blastema formation and growth. We have identified a novel newt chemokine, NvCXCL, that is highly upregulated during limb regeneration and may play a role in this process. NvCXCL is expressed in de-differentiating tissues and the blastema, stimulates cells of mouse fibroblastic and myoblastic cell lines to proliferate, and mildly induces the mouse fibroblasts to migrate, although not in a directed fashion. This work establishes a detailed baseline of the events occurring during spinal cord regeneration and identifies a novel chemokine that may be involved in the formation and growth of the limb blastema. Further insights into the mechanisms driving limb and spinal cord regeneration will be greatly aided by the development of more powerful genetic tools. If the dream of regenerative medicine is to become a reality, it is imperative that we learn all we can about how nature has already derived a solution for regenerating injured structures and organs in this exceptional animal. |
