Fgf-dependent glial cell bridges facilitate spinal cord regeneration in zebrafish.
Adult zebrafish show a remarkable capacity to regenerate their spinal column after injury, an ability that stands in stark contrast to the limited repair that occurs within the mammalian CNS post-injury. The reasons for this interspecies difference in regenerative capacity remain unclear. Here we demonstrate a novel role for Fgf signaling during glial cell morphogenesis in promoting axonal regeneration after spinal cord injury. Zebrafish glia are induced by Fgf signaling, to form an elongated bipolar morphology that forms a bridge between the two sides of the resected spinal cord, over which regenerating axons actively migrate. Loss of Fgf function inhibits formation of this "glial bridge" and prevents axon regeneration. Despite the poor potential for mammalian axonal regeneration, primate astrocytes activated by Fgf signaling adopt a similar morphology to that induced in zebrafish glia. This suggests that differential Fgf regulation, rather than intrinsic cell differences, underlie the distinct responses of mammalian and zebrafish glia to injury.
Australian Regenerative Medicine Institute, Monash University, Clayton, Victoria 3800, Australia. yona.goldshmit@med.monash.edu.au
Yona
Y
Goldshmit
Tamar E
TE
Sztal
Patricia R
PR
Jusuf
Thomas E
TE
Hall
Mai
M
Nguyen-Chi
Peter D
PD
Currie
D000704:Analysis of Variance; D000818:Animals; D030801:Animals, Genetically Modified; D001973:Bromodeoxyuridine / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D003911:Dextrans; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D051518:Fibroblast Growth Factor 3 / Q000235:genetics / Q000378:metabolism; D051524:Fibroblast Growth Factor 8 / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D007381:Intermediate Filament Proteins / Q000235:genetics / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D020929:Mitogen-Activated Protein Kinase Kinases / Q000235:genetics / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects / Q000235:genetics; D009416:Nerve Regeneration / Q000187:drug effects / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D064231:Nestin; D009457:Neuroglia / Q000187:drug effects / Q000502:physiology*; D011758:Pyrroles / Q000494:pharmacology; D012333:RNA, Messenger; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics; D020127:Recovery of Function; D012235:Rhodamines; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics*; D013119:Spinal Cord Injuries / Q000473:pathology* / Q000503:physiopathology*; D013997:Time Factors; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism
D003911:Dextrans; D004791:Enzyme Inhibitors; C496456:FGF8 protein, human; D051518:Fibroblast Growth Factor 3; C067661:Fluoro-Ruby; D005904:Glial Fibrillary Acidic Protein; D007381:Intermediate Filament Proteins; D019394:Ki-67 Antigen; C577484:NES protein, human; D009419:Nerve Tissue Proteins; D064231:Nestin; D011758:Pyrroles; D012333:RNA, Messenger; D012235:Rhodamines; C105686:SU 5402; D029961:Zebrafish Proteins; C489200:fgf3 protein, zebrafish; C434248:spry4 protein, zebrafish; D016222:Fibroblast Growth Factor 2; D049452:Green Fluorescent Proteins; D051524:Fibroblast Growth Factor 8; D051496:Receptor, Fibroblast Growth Factor, Type 1; D020929:Mitogen-Activated Protein Kinase Kinases; D001973:Bromodeoxyuridine