Roles for Fgf signaling during zebrafish fin regeneration

Following amputation of a urodele limb or teleost fin, the formation of a b lastema is a crucial step in facilitating subsequent regeneration. Using th e 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 exp ressed in mesenchymal cells underlying the wound epidermis during blastema formation and in distal blastemal tissue during regenerative outgrowth. fgf r1 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. Furtherm ore, we show that a specific inhibitor of Fgfr1 applied immediately followi ng fin amputation blocks blastema formation, without obvious effects on wou nd healing. This inhibitor blocks the proliferation of blastemal cells and the onset of msx gene transcription. Inhibition of Fgf signaling during ong oing fin regeneration prevents further outgrowth while downregulating the e stablished expression of blastemal msx genes and epidermal sonic hedgehog. Our findings indicate that zebrafish fin blastema formation and regenerativ e outgrowth require Fgf signaling, (C) 2000 Academic Press.