Roles for Fgf signaling during zebrafish fin regeneration.
Following amputation of a urodele limb or teleost fin, the formation of a blastema is a crucial step in facilitating subsequent regeneration. Using the zebrafish caudal fin regeneration model, we have examined the hypothesis that fibroblast growth factors (Fgfs) initiate blastema formation from fin mesenchyme. We find that fibroblast growth factor receptor 1 (fgfr1) is expressed in mesenchymal cells underlying the wound epidermis during blastema formation and in distal blastemal tissue during regenerative outgrowth. fgfr1 transcripts colocalize with those of msxb and msxc, putative markers for undifferentiated, proliferating cells. A zebrafish Fgf member, designated wfgf, is expressed in the regeneration epidermis during outgrowth. Furthermore, we show that a specific inhibitor of Fgfr1 applied immediately following fin amputation blocks blastema formation, without obvious effects on wound healing. This inhibitor blocks the proliferation of blastemal cells and the onset of msx gene transcription. Inhibition of Fgf signaling during ongoing fin regeneration prevents further outgrowth while downregulating the established expression of blastemal msx genes and epidermal sonic hedgehog. Our findings indicate that zebrafish fin blastema formation and regenerative outgrowth require Fgf signaling.
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Howard Hughes Medical Institute, Eccles Institute of Human Genetics, University of Utah Health Sciences Center, 15N 2030E, Salt Lake City, Utah, 84112, USA.
Shen
J
J
Nechiporuk
A
A
McMahon
G
G
Thisse
B
B
Thisse
C
C
Keating
M T
MT
D000671:Amputation, Surgical; D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004817:Epidermis / Q000502:physiology; D005121:Extremities / Q000502:physiology*; D005346:Fibroblast Growth Factors / Q000502:physiology*; D008648:Mesoderm / Q000502:physiology; D011758:Pyrroles / Q000494:pharmacology; D020794:Receptor Protein-Tyrosine Kinases / Q000187:drug effects / Q000502:physiology*; D051496:Receptor, Fibroblast Growth Factor, Type 1; D017468:Receptors, Fibroblast Growth Factor / Q000187:drug effects / Q000502:physiology*; D012038:Regeneration / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction; D015027:Zebrafish
D004791:Enzyme Inhibitors; D011758:Pyrroles; D017468:Receptors, Fibroblast Growth Factor; C105686:SU 5402; D005346:Fibroblast Growth Factors; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1