Researchers have pinpointed key molecules that prompt damaged nerve fibers in zebrafish to regenerate themselves. Nerve fibers (arrows) can be seen crossing an injury site in the spinal cord of a living zebrafish. [University of Edinburgh]

Researchers at the University of Edinburgh's Centre for Neuroregeneration Researchers say they have found the molecules that lead damaged nerve fibers to regenerate in zebrafish. The discovery could open the door to new therapies that help relink the connections between the brain and muscles that are lost after spinal cord injury in people.

Zebrafish can regain full movement within a month of injury to their spinal cord because they are able to restore damaged connections and nerve cells in the cord.

The scientists report (“Wnt Signaling Controls Pro-Regenerative Collagen XII in Functional Spinal Cord Regeneration in Zebrafish”) in Nature Communications that they have located an important mechanism that helps the nerve connections to regrow in zebrafish. They noted that after injury, fibroblasts move into the site of damage and produce collagen XII, which changes the structure of the support matrix that surrounds nerve fibers. This enables the damaged fibers to grow back across the wound site and restore the lost connections.

“We demonstrate that in a vertebrate of high regenerative capacity, Wnt/β-catenin signaling controls the composition of the lesion site extracellular matrix and we identify Collagen XII as a promoter of axonal regeneration,” write the investigators. “These findings imply that the Wnt/β-catenin pathway and Collagen XII may be targets for extracellular matrix manipulations in non-regenerating species.”

The team found that fibroblasts are instructed to make collagen XII by a chemical signal known as Wnt. Understanding these signals could hold clues for treatments to help heal the spinal cord after injury, according to the researchers.

“In people and other mammals, the matrix in the injury site blocks nerves from growing back after an injury,” explains Thomas Becker, Ph.D., of the Centre for Neuroregeneration. “We have now pinpointed the signals that remove this roadblock in zebrafish, so that nerve cells can repair connections that are lost after damage to the spinal cord.”

“We next plan to check whether triggering these signals in other animals can help them to repair nerve connections damaged by spinal cord injuries.”

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