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

doi:10.1038/CDDIS.2017.374

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

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

91 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 language	English
Article number	e2979
Journal	Cell Death and Disease
Volume	8
Issue number	8
DOIs	https://doi.org/10.1038/CDDIS.2017.374
State	Published - Aug 2017
Externally published	Yes

Bibliographical note

Funding Information:
Acknowledgements. This work was supported by Inserm and grants from ‘Région Languedoc-Roussillon, Chercheur d’Avenir’ no. DGA3/DESR 2012/Q209, from the French National Research Agency ‘Zebraflam’ no. ANR-10-MIDI-009 and from the European Community’s Seventh Framework Program (FP7-PEOPLE-2011-ITN) under the Marie-Curie Initial Training Network FishForPharma (Grant Agreement No. PITN-GA-2011-289209). We thank the MRI facility for their assistance, J-P. Levraud (Institut Pasteur, France) for trans-shipping Tg(mpeg:Gal4;UAS:NTR-mCherry) line, A. Kawakami (Tokyo Institute of Technology, Japan) for junbl probe, M. Bagnat for tg(rcn3:gal4/UAS:dsRed) line and E. Lelièvre (Université de Montpellier, Montpellier) for providing support and advice during parabiosis experiments.

Publisher Copyright:
© The Author(s) 2017.

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10.1038/CDDIS.2017.374

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@article{7894cf80732b4e25ae401fb4d6a8bc68,

title = "TNF signaling and macrophages govern fin regeneration in zebrafish larvae",

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.",

author = "Mai Nguyen-Chi and B{\'e}ryl Laplace-Builh{\'e} and Jana Travnickova and Patricia Luz-Crawford and Gautier Tejedor and Georges Lutfalla and Karima Kissa and Christian Jorgensen and Farida Djouad",

note = "Funding Information: Acknowledgements. This work was supported by Inserm and grants from {\textquoteleft}R{\'e}gion Languedoc-Roussillon, Chercheur d{\textquoteright}Avenir{\textquoteright} no. DGA3/DESR 2012/Q209, from the French National Research Agency {\textquoteleft}Zebraflam{\textquoteright} no. ANR-10-MIDI-009 and from the European Community{\textquoteright}s Seventh Framework Program (FP7-PEOPLE-2011-ITN) under the Marie-Curie Initial Training Network FishForPharma (Grant Agreement No. PITN-GA-2011-289209). We thank the MRI facility for their assistance, J-P. Levraud (Institut Pasteur, France) for trans-shipping Tg(mpeg:Gal4;UAS:NTR-mCherry) line, A. Kawakami (Tokyo Institute of Technology, Japan) for junbl probe, M. Bagnat for tg(rcn3:gal4/UAS:dsRed) line and E. Leli{\`e}vre (Universit{\'e} de Montpellier, Montpellier) for providing support and advice during parabiosis experiments. Publisher Copyright: {\textcopyright} The Author(s) 2017.",

year = "2017",

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doi = "10.1038/CDDIS.2017.374",

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AU - Nguyen-Chi, Mai

AU - Laplace-Builhé, Béryl

AU - Travnickova, Jana

AU - Luz-Crawford, Patricia

AU - Tejedor, Gautier

AU - Lutfalla, Georges

AU - Kissa, Karima

AU - Jorgensen, Christian

AU - Djouad, Farida

N1 - Funding Information: Acknowledgements. This work was supported by Inserm and grants from ‘Région Languedoc-Roussillon, Chercheur d’Avenir’ no. DGA3/DESR 2012/Q209, from the French National Research Agency ‘Zebraflam’ no. ANR-10-MIDI-009 and from the European Community’s Seventh Framework Program (FP7-PEOPLE-2011-ITN) under the Marie-Curie Initial Training Network FishForPharma (Grant Agreement No. PITN-GA-2011-289209). We thank the MRI facility for their assistance, J-P. Levraud (Institut Pasteur, France) for trans-shipping Tg(mpeg:Gal4;UAS:NTR-mCherry) line, A. Kawakami (Tokyo Institute of Technology, Japan) for junbl probe, M. Bagnat for tg(rcn3:gal4/UAS:dsRed) line and E. Lelièvre (Université de Montpellier, Montpellier) for providing support and advice during parabiosis experiments. Publisher Copyright: © The Author(s) 2017.

PY - 2017/8

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N2 - 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.

AB - 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.

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DO - 10.1038/CDDIS.2017.374

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AN - SCOPUS:85029923779

SN - 2041-4889

VL - 8

JO - Cell Death and Disease

JF - Cell Death and Disease

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ER -

TNF signaling and macrophages govern fin regeneration in zebrafish larvae

Abstract

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