Fgf signalling controls diverse aspects of fin regeneration

Abstract

Studies have shown that fibroblast growth factor (Fgf ) signalling is necessary for appendage regeneration, but its exact function and the ligands involved during regeneration have not yet been elucidated. Here, we performed comprehensive expression analyses and identified fgf20a and fgf3/10a as major Fgf ligands in the wound epidermis and blastema, respectively. To reveal the target cells and processes of Fgf signalling, we performed a transplantation experiment of mesenchymal cells that express the dominantnegative Fgf receptor 1 (dnfgfr1) under control of the heat-shock promoter. This mosaic knockdown analysis suggested that Fgf signalling is directly required for fin ray mesenchyme to form the blastema at the early pre-blastema stage and to activate the regenerative cell proliferation at a later post-blastema stage. These results raised the possibility that the early epidermal Fgf20a and the later blastemal Fgf3/10a could be responsible for these respective processes. We demonstrated by gain-of-function analyses that Fgf20a induces the expression of distal blastema marker junbl, and that Fgf3 promotes blastema cell proliferation. Our study highlights that Fgfs in the wound epidermis and blastema have distinct functions to regulate fin regeneration cooperatively.

Transient inflammatory response mediated by interleukin-1β is required for proper regeneration in zebrafish fin fold

“…Compared with WT larvae, the clo larvae showed marked upregulation of regeneration-induced genes such as junba , junbb , matrix metallopeptidase 9 ( mmp9 ), fibronectin 1b ( fn1b ), and fgf20a (Yoshinari et al, 2009; Shibata et al, 2016) (Figure 1A and Supplementary file 1). In addition to these genes, expression of a group of genes including il1b and tumor necrosis factor-b ( tnfb ), which are involved in the inflammatory response, was also upregulated in the clo mutant during fin fold regeneration.…”

“…The Dex-treated larvae displayed apparent retardation of regeneration at 3 dpa (Figure 7A and B) and a statistically significant reduction in cell proliferation in the distal fin fold region (Figure 7C and D). Notably, the expression of regeneration-induced genes such as junba (Yoshinari et al, 2009) and fgf20a (Whitehead et al, 2005; Shibata et al, 2016) was downregulated in the Dex-treated larvae (Figure 7E). These data suggest that inflammation is required for activation of regeneration-induced gene expression which is a prerequisite for normal regeneration.

10.7554/eLife.22716.016Figure 7.Il1b-mediated inflammation is required for normal regeneration.( A ) Fin fold regeneration in WT larvae treated with Dex.

…”

“…BrdU-positive cells were significantly reduced following Dex treatment. ( E ) Detection of junba expression using ISH and fgf20a expression using the HGn21A enhancer-trap line (Shibata et al, 2016) in DMSO- or Dex-treated larvae. The expression of junba and fgf20a was also significantly downregulated following Dex treatment.…”

Transposons As Tools for Functional Genomics in Vertebrate Models

“…7). Since the body of a zebrafish larva is transparent through all developmental stages, such transgenic fish have been used to visualize the vascular system [108], the central and peripheral nervous systems [109, 110], the regenerating processes of the sensory system and fin [111, 112], the cellular process of muscle wound repair [113], and proteolytic cleavage of the extracellular domain of a membrane protein (Neuregulin) in the motor neurons [114], among others. Also, the transgenic fish were applied to image the activity of specific neuronal populations or endothelial cells by targeted expression of a calcium indicator GCaMP [115, 116].…”

“…( D ) Lateral line glial cells in gSAGFF202A at 5 dpf [111]. ( E ) Caudal trunk (and the wound epidermis) in HGn21A embryo at 1 dpf [112]. ( F ) Fgf7b-positive muscle cells in gSAIzGFFD164A at 1 dpf [113].…”