Injury-induced ctgfa directs glial bridging and spinal cord regeneration in zebrafish.
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.
Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA.
Mayssa H
MH
Mokalled
Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research, 61231 Bad Nauheim, Germany.
Chinmoy
C
Patra
Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA.
Amy L
AL
Dickson
Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA.
Toyokazu
T
Endo
Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research, 61231 Bad Nauheim, Germany.
Didier Y R
DY
Stainier
Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA. kenneth.poss@duke.edu.
Kenneth D
KD
Poss
D000818:Animals; D030801:Animals, Genetically Modified; D055513:Connective Tissue Growth Factor / Q000235:genetics / Q000502:physiology*; D005260:Female; D008297:Male; D009154:Mutation; D009457:Neuroglia / Q000502:physiology*; D013119:Spinal Cord Injuries / Q000503:physiopathology*; D058630:Spinal Cord Regeneration / Q000235:genetics; D015027:Zebrafish / Q000235:genetics / Q000502:physiology*; D029961:Zebrafish Proteins / Q000235:genetics / Q000502:physiology*
D029961:Zebrafish Proteins; C000617634:ccn2a protein, zebrafish; D055513:Connective Tissue Growth Factor