Healing protein at spinal cord injured zebrafish

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Mammals cannot regenerate their complex nervous tissue but small, tropical zebrafish can repair a severed spine in eight weeks. Researchers found a special growth protein responsible for this healing and repair.

What do we know so far?
Mammals are not capable of regenerating complex nervous tissue after a severe spinal cord injury, which can often cause paralysis. However, a small, tropical freshwater fish native to South East Asia called zebrafish has the ability to rapidly regenerate their nervous tissue.
When a zebrafish is injured, a bridge of supporting glial cells forms between the two ends. These cells extend from both sides of the injury over distances ten times their own length to reach across and finally form the bridge.
Neuronal cells then follow along the supporting cell bridge and after only eight weeks, enough tissue has been built to completely reverse the paralysis.

What are the results of the study?
Scientists from the Duke University analyzed all of the zebrafish genes whose activity suddenly changed immediately following a spinal injury. Their attention focused on a particular gene whose activity levels specifically rose in the supporting cells that formed the bridge in the first two weeks following injury. This particular gene encodes for a protein called connective tissue growth factor or CTGF. When scientists tried deleting CTGF genetically, those fish failed to regenerate.
We (humans) share 70 per cent of our genetic code with zebrafish, and the human CTGF protein is nearly 90% similar to the one from the zebrafish. When the team added the human version of CTGF to the injury site in fish, it boosted regeneration and the fish swam better by two weeks after the injury.

What will happen next?
CTGF is a large protein, made of four smaller parts, and it has more than one function. But the second half of the CTGF protein seems to be the key to the healing, so shrinking it to only this segment might make it easier to deliver as potential therapy for spinal injuries.

CTGF alone is unlikely to be sufficient in humans to regenerate lost tissue after a spinal injury. More experiments on different models are needed to see if CTGF has any potential for human application.
The group also plans to follow up on other proteins secreted after injury that were identified in their initial search, which may provide additional hints into the zebrafish’s secrets of regeneration.


Source: “Injury-induced ctgfa directs glial bridging and spinal cord regeneration in zebrafish,” Mayssa H. Mokalled, Chinmoy Patra, Amy L. Dickson, Toyokazu Endo, Didier Y. R. Stainier, Kenneth D. Poss. Science, November 4, 2016. And “Building bridges to regenerate axons” Williams PR, He Z. Science. 2016 Nov 4; 544-545.