Dynamic control of proinflammatory cytokines Il-1β and Tnf-α by macrophages in zebrafish spinal cord regeneration
Themistoklis M. Tsarouchas,
Daniel Wehner,
Leonardo Cavone,
Tahimina Munir,
Marcus Keatinge,
Marvin Lambertus,
Anna Underhill,
Thomas Barrett,
Elias Kassapis,
Nikolay Ogryzko,
Yi Feng,
Tjakko J. van Ham,
Thomas Becker,
Catherina G. Becker
Nature Communications
9
4670
(2018)
| Journal
| PDF
Spinal cord injury leads to a massive response of innate immune cells in non-regenerating mammals, but also in successfully regenerating zebrafish. However, the role of the immune response in successful regeneration is poorly defined. Here we show that inhibiting inflammation reduces and promoting it accelerates axonal regeneration in spinal-lesioned zebrafish larvae. Mutant analyses show that peripheral macrophages, but not neutrophils or microglia, are necessary for repair. Macrophage-less irf8 mutants show prolonged inflammation with elevated levels of Tnf-alpha and Il-1 beta. Inhibiting Tnf-a does not rescue axonal growth in irf8 mutants, but impairs it in wildtype animals, indicating a pro-regenerative role of Tnf-a. In contrast, decreasing Il-1 beta levels or number of Il-1 beta+ neutrophils rescue functional regeneration in irf8 mutants. However, during early regeneration, interference with Il-1 beta function impairs regeneration in irf8 and wildtype animals. Hence, inflammation is dynamically controlled by macrophages to promote functional spinal cord regeneration in zebrafish.
Restoration of anatomical continuity after spinal cord transection depends on Wnt/beta-catenin signaling in larval zebrafish
This data article contains descriptive and experimental data on spinal cord regeneration in larval zebrafish and its dependence on Wnt/beta-catenin signaling. Analyzing spread of intraspinally injected fluorescent dextran showed that anatomical continuity is rapidly restored after complete spinal cord transection. Pharmacological interference with Wnt/beta-catenin signaling (IWR-1) impaired restoration of spinal continuity. For further details and experimental findings please refer to the research article by Wehner et al. Wnt signaling controls pro-regenerative Collagen XII in functional spinal cord regeneration in zebrafish (Wehner et al., 2017) [1]. (C) 2017 The Authors. Published by Elsevier Inc.
Contact
Research Group Daniel Wehner
Max-Planck-Zentrum für Physik und Medizin Kussmaulallee 2 91054 Erlangen, Germany
