image: Adult zebrafish are capable of regenerating their spinal cords after complete transection injury. Expression of the<i> connective tissue growth factor a (ctgfa) </i>gene in tissue that is bridging the two severed ends stimulates spinal cord regeneration. Glial cells are indicated in red, neuronal cells in green, and ependymal cells in blue. Zebrafish provide a model to inform methodologies for spinal cord regeneration in humans. view more
Credit: M. Mokalled and K. Poss
Researchers have identified a protein in zebrafish that facilitates healing of major spinal cord injuries. While mammals lack the ability to regenerate nervous system tissue after spinal cord injury, zebrafish can regenerate such tissue. Yet, the mechanisms behind this recovery have remained elusive. Scientists have thought clues may exist in glial cells, which, in mammals, cause scarring that interferes with spinal cord repair; in zebrafish, however, these same cells help create a bridge across severed spinal cord tissue and facilitate regeneration. To gain more insights into this capacity in zebrafish, Mayssa Mokalled and colleagues analyzed their gene expression following spinal cord injury, identifying seven genes of interest. Of these, connective tissue growth factor a (ctgfa), was found to be expressed during a key period of healing, as glial cells were actively building bridges across damaged tissue. Zebrafish in which ctgfa was knocked out exhibited glial cells that often failed to extend into the lesions, and the fish were unable to recover from spinal injury. In contrast, overexpression of ctgfa resulted in increased bridging, axon regeneration, and overall healing compared to controls. When the researchers applied a human form of CTGF protein to lesions in zebrafish, similar recovery of spinal cord function was observed, hinting that other factors within zebrafish spinal tissue may explain the healing differences between mammals and zebrafish; Philip Williams and Zhigang He explore some possible explanations for these differences in a related Perspective.
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Journal
Science