TNF signaling and macrophages govern fin regeneration in zebrafish larvae

Mai Nguyen-Chi, Béryl Laplace-Builhé, Jana Travnickova, Patricia Luz-Crawford, Gautier Tejedor, Georges Lutfalla, Karima Kissa, Christian Jorgensen, Farida Djouad

Research output: Contribution to journalArticlepeer-review

42 Scopus citations

Abstract

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.
Original languageAmerican English
Pages (from-to)e2979
Number of pages1
JournalCell death & disease
Volume8
Issue number8
DOIs
StatePublished - 10 Aug 2017
Externally publishedYes

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