Nguyen-Chi Mai, Laplace-Builhé Béryl, Travnickova Jana, Luz-Crawford Patricia, Tejedor Gautier, Lutfalla Georges, Kissa Karima, Jorgensen Christian, Djouad Farida
IRMB, INSERM, Univ Montpellier, Montpellier, France.
DIMNP, CNRS, Univ Montpellier, Montpellier, France.
Cell Death Dis. 2017 Aug 10;8(8):e2979. doi: 10.1038/cddis.2017.374.
Macrophages are essential for appendage regeneration after amputation in regenerative species. The molecular mechanisms through which macrophages orchestrate blastema formation and regeneration are still unclear. Here, we use the genetically tractable and transparent zebrafish larvae to study the functions of polarized macrophage subsets during caudal fin regeneration. After caudal fin amputation, we show an early and transient accumulation of pro-inflammatory macrophages concomitant with the accumulation of non-inflammatory macrophages which, in contrast to pro-inflammatory macrophages, remain associated to the fin until the end of the regeneration. Chemical and genetic depletion of macrophages suggested that early recruited macrophages that express TNFα are critical for blastema formation. Combining parabiosis and morpholino knockdown strategies, we show that TNFα/TNFR1 signaling pathway is required for the fin regeneration. Our study reveals that TNFR1 has a necessary and direct role in blastema cell activation suggesting that macrophage subset balance provides the accurate TNFα signal to prime regeneration in zebrafish.
巨噬细胞对于再生物种截肢后的附肢再生至关重要。巨噬细胞协调芽基形成和再生的分子机制仍不清楚。在这里，我们使用基因易处理且透明的斑马鱼幼虫来研究极化巨噬细胞亚群在尾鳍再生过程中的功能。尾鳍截肢后，我们发现促炎性巨噬细胞早期短暂积累，同时非炎性巨噬细胞也积累，与促炎性巨噬细胞不同的是，非炎性巨噬细胞在再生结束前一直与鳍相连。巨噬细胞的化学和基因缺失表明，早期招募的表达TNFα的巨噬细胞对芽基形成至关重要。结合联体生活和吗啉代敲低策略，我们表明鳍再生需要TNFα/TNFR1信号通路。我们的研究表明，TNFR1在芽基细胞激活中具有必要且直接作用，这表明巨噬细胞亚群平衡为启动斑马鱼再生提供了精确的TNFα信号。
