ZFIN ID: ZDB-PUB-170811-2
TNF signaling and macrophages govern fin regeneration in zebrafish larvae
Nguyen-Chi, M., Laplace-Builhé, B., Travnickova, J., Luz-Crawford, P., Tejedor, G., Lutfalla, G., Kissa, K., Jorgensen, C., Djouad, F.
Date: 2017
Source: Cell Death & Disease   8: e2979 (Journal)
Registered Authors:
Keywords: none
MeSH Terms:
  • Animals
  • Animals, Genetically Modified
  • Extremities/embryology
  • Extremities/physiology
  • Larva/genetics
  • Larva/metabolism*
  • Macrophages/metabolism
  • Receptors, Tumor Necrosis Factor, Type I/genetics
  • Receptors, Tumor Necrosis Factor, Type I/metabolism
  • Regeneration/genetics
  • Regeneration/physiology
  • Signal Transduction/genetics
  • Signal Transduction/physiology*
  • Tumor Necrosis Factor-alpha/metabolism*
  • Zebrafish/genetics
  • Zebrafish/metabolism*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
PubMed: 28796253 Full text @ Cell Death Dis.
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.