Fgf signalling controls diverse aspects of fin regeneration
Fgf signalling controls diverse aspects of fin regeneration
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DOI：
10.1242/dev.140699
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发表时间：
2016-08-15
期刊：
影响因子：
4.6
通讯作者：
Kawakami, Atsushi
中科院分区：
文献类型：
--
作者：
Shibata, Eri;Yokota, Yuki;Kawakami, Atsushi
研究表明，成纤维细胞生长因子(成纤维细胞生长因子)信号是附件再生所必需的，但其确切功能和再生过程中涉及的配体尚不清楚。在这里，我们进行了全面的表达分析，并确定fgf20a和fgf3/10a分别是伤口表皮和胚泡中的主要成纤维细胞生长因子配体。为了揭示成纤维细胞生长因子信号转导的靶细胞和过程，我们在热休克启动子的控制下，对表达显性负向成纤维细胞生长因子受体1(Dnfgfr1)的间充质细胞进行了移植实验。这一嵌合敲除分析表明，鳍射线间充质细胞在胚泡早期形成胚泡和在胚泡后期激活再生细胞增殖直接需要成纤维细胞生长因子信号。这些结果提出了早期表皮Fgf20a和晚期胚泡Fgf3/10a可能分别负责这些过程的可能性。我们通过功能增益分析证明，Fgf20a诱导胚泡远端标志Junb1的表达，并且Fgf3促进胚泡细胞的增殖。我们的研究强调，伤口表皮和胚泡中的FGFs具有不同的功能，协同调节FIN的再生。
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.