Injury-induced ctgfa directs glial bridging and spinal cord regeneration in zebrafish

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Science  04 Nov 2016:
Vol. 354, Issue 6312, pp. 630-634
DOI: 10.1126/science.aaf2679

Spinal cord regeneration in zebrafish

Unlike humans, zebrafish can regenerate their spinal cord. Mokalled et al. identified a growth factor in zebrafish that helps this process (see the Perspective by Williams and He). The protein encoded by ctgfa (connective tissue growth factor a) is secreted after injury and encourages glial cells to form a bridge across the spinal lesion. Addition of this protein improved spinal cord repair in injured zebrafish.

Science, this issue p. 630; see also p. 544


Unlike mammals, zebrafish efficiently regenerate functional nervous system tissue after major spinal cord injury. Whereas glial scarring presents a roadblock for mammalian spinal cord repair, glial cells in zebrafish form a bridge across severed spinal cord tissue and facilitate regeneration. We performed a genome-wide profiling screen for secreted factors that are up-regulated during zebrafish spinal cord regeneration. We found that connective tissue growth factor a (ctgfa) is induced in and around glial cells that participate in initial bridging events. Mutations in ctgfa disrupted spinal cord repair, and transgenic ctgfa overexpression or local delivery of human CTGF recombinant protein accelerated bridging and functional regeneration. Our study reveals that CTGF is necessary and sufficient to stimulate glial bridging and natural spinal cord regeneration.

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