title: 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 dominant-negative 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.
authors.affiliation: Department of Biological Information, Tokyo Institute of Technology, 4259 Nagatsuta, Midori-ku, Yokohama 226-8501, Japan.
authors.forename: Eri
authors.initials: E
authors.lastname: Shibata
authors.affiliation: Department of Biological Information, Tokyo Institute of Technology, 4259 Nagatsuta, Midori-ku, Yokohama 226-8501, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Yokota
authors.affiliation: Department of Biological Information, Tokyo Institute of Technology, 4259 Nagatsuta, Midori-ku, Yokohama 226-8501, Japan.
authors.forename: Natsumi
authors.initials: N
authors.lastname: Horita
authors.affiliation: Department of Biological Information, Tokyo Institute of Technology, 4259 Nagatsuta, Midori-ku, Yokohama 226-8501, Japan.
authors.forename: Akira
authors.identifier: 0000-0001-9461-6372
authors.initials: A
authors.lastname: Kudo
authors.affiliation: Division of Molecular and Developmental Biology, National Institute of Genetics, Mishima 411-8540, Japan.
authors.forename: Gembu
authors.initials: G
authors.lastname: Abe
authors.affiliation: Division of Molecular and Developmental Biology, National Institute of Genetics, Mishima 411-8540, Japan Department of Genetics, SOKENDAI (The Graduate University for Advanced Studies), Mishima, 411-8540, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Kawakami
authors.affiliation: Department of Biological Information, Tokyo Institute of Technology, 4259 Nagatsuta, Midori-ku, Yokohama 226-8501, Japan atkawaka@bio.titech.ac.jp.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kawakami
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000235:genetics / Q000502:physiology; D051518:Fibroblast Growth Factor 3 / Q000235:genetics / Q000378:metabolism*; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D051518:Fibroblast Growth Factor 3; D029961:Zebrafish Proteins; C489200:fgf3 protein, zebrafish; C503561:fibroblast growth factor 20, zebrafish; C479567:fibroblast growth factor 24, zebrafish; D005346:Fibroblast Growth Factors
keywords: Blastema; Fgf; Fin regeneration; Wound epidermis; Zebrafish