A switch in pdgfrb+ cell-derived ECM composition prevents inhibitory scarring and promotes axon regeneration in the zebrafish spinal cord
Tsata V, Schweitzer C, Kolb J, Moeckel C, Boehm B, Rosso G, Lange C, Lesche M, Hammer J, Kesavan G, Beis D, Guck J, Brand M, Wehner D, Möllmert S (2021)
Publication Type: Journal article
Publication year: 2021
Journal
Book Volume: 56
Pages Range: 509-524.e9
Journal Issue: 4
DOI: 10.1016/j.devcel.2020.12.009
Abstract
In mammals, perivascular cell-derived scarring after spinal cord injury impedes axonal regrowth. In contrast, the extracellular matrix (ECM) in the spinal lesion site of zebrafish is permissive and required for axon regeneration. However, the cellular mechanisms underlying this interspecies difference have not been investigated. Here, we show that an injury to the zebrafish spinal cord triggers recruitment of pdgfrb+ myoseptal and perivascular cells in a PDGFR signaling-dependent manner. Interference with pdgfrb+ cell recruitment or depletion of pdgfrb+ cells inhibits axonal regrowth and recovery of locomotor function. Transcriptional profiling and functional experiments reveal that pdgfrb+ cells upregulate expression of axon growth-promoting ECM genes (cthrc1a and col12a1a/b) and concomitantly reduce synthesis of matrix molecules that are detrimental to regeneration (lum and mfap2). Our data demonstrate that a switch in ECM composition is critical for axon regeneration after spinal cord injury and identify the cellular source and components of the growth-promoting lesion ECM.In mammals, perivascular cells impede axon regeneration after spinal cord injury through secretion of an inhibitory ECM. Tsata et al. show that in the regeneration-competent zebrafish, myoseptal and perivascular cells promote axon regeneration by depositing a growth-promoting ECM that is deprived of growth-inhibitory matrix molecules.
Authors with CRIS profile
Involved external institutions
Technische Universität Dresden
Germany (DE)
Max-Planck-Institut für die Physik des Lichts (MPL) / Max Planck Institute for the Science of Light
Germany (DE)
Academy of Athens / Ακαδημία Αθηνών
Greece (GR)
Germany (DE)
Max-Planck-Institut für die Physik des Lichts (MPL) / Max Planck Institute for the Science of Light
Germany (DE)
Academy of Athens / Ακαδημία Αθηνών
Greece (GR)
How to cite
APA:
Tsata, V., Schweitzer, C., Kolb, J., Moeckel, C., Boehm, B., Rosso, G.,... Möllmert, S. (2021). A switch in pdgfrb+ cell-derived ECM composition prevents inhibitory scarring and promotes axon regeneration in the zebrafish spinal cord. Developmental Cell, 56(4), 509-524.e9. https://doi.org/10.1016/j.devcel.2020.12.009
MLA:
Tsata, Vasiliki, et al. "A switch in pdgfrb+ cell-derived ECM composition prevents inhibitory scarring and promotes axon regeneration in the zebrafish spinal cord." Developmental Cell 56.4 (2021): 509-524.e9.
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