Researchers are one step closer to solving the mystery of why some vertebrates can regenerate their spinal cords while others, including humans, create scar tissue after spinal-cord injury (SCI), leading to lifelong damage.
Scientists at the Marine Biological Laboratory in Massachusetts have identified gene "partners" in the axolotl salamander that, when activated, allow the neural tube and associated nerve fibers to functionally regenerate after severe spinal-cord damage. These genes are also present in humans, though they are activated in a different manner. Their results are published in March's Nature Communications Biology.
"[Axolotls are] the champions of regeneration in that they can regenerate multiple body parts. For example, if you make a lesion in the spinal cord, they can fully regenerate it and gain back both motor and sensory control," says Karen Echeverri, associate scientist in the Eugene Bell Center for Regenerative Biology and Tissue Engineering in Woods Hole, Mass. "We wanted to understand what is different at a molecular level that drives them towards this pro-regenerative response instead of forming scar tissue."
Echeverri's prior research had shown that, in both axolotls and humans, the c-Fos gene is up-regulated in the glial cells of the nervous system after SCI. She also knew that c-Fos cannot act alone.
In human injury response, c-Fos is paired with the gene c-Jun. In axolotls, however, Echeverri and her team determined that c-Fos is activated with the gene JunB. This difference in gene activation was traced to the actions of microRNAs, which regulate gene expression.
By modifying gene expression by the axolotls' microRNA, they forced the human pairing of c-Fos with c-Jun. The salamanders with the human pairings couldn't regain a functioning spinal cord after injury, instead forming the scar tissue that occurs in human injury repair. Follow-up studies will investigate if the reverse is true in human cells.
Adapted from materials provided by the Marine Biological Laboratory.
Caption: Axolotyl tanks in Karen Echeverri's laboratory.
Caption: Axolotls with natural differences in pigmentation in Karen Echeverri's laboratory.
Caption: Karen Echeverri is an associate scientist in the Marine Biological Laboratory's Eugene Bell Center for Regenerative Biology and Tissue Engineering.