PREreviews of “Macrophage crosstalk with neural progenitors and fibroblasts controls regenerative neurogenesis via Sema4ab after spinal cord injury in zebrafish”

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Macrophage crosstalk with neural progenitors and fibroblasts controls regenerative neurogenesis via Sema4ab after spinal cord injury in zebrafish

by Alberto Docampo-Seara, Mehmet Ilyas Cosacak, Kim Heilemann, Friederike Kessel, Ana-Maria Oprişoreanu, Özge Çark, Daniela Zöller, Josi Arnold, Anja Bretschneider, Alisa Hnatiuk, Nikolay Ninov, Catherina G. Becker, and Thomas Becker

Posted: October 18, 2024
Server: bioRxiv
DOI: 10.1101/2024.10.16.618445

Abstract

After spinal cord injury, interactions of multiple tissues inhibit neuronal regeneration in mammals, but not in anamniotes, such as zebrafish. These pivotal interactions are poorly understood. Here we analyse the role of the cell signalling moleculesema4abin the cell communication network leading to regenerative neurogenesis after spinal injury in larval zebrafish.Sema4abis expressed by macrophages and gene ablation doubles the rate of regenerative neurogenesis. Disruption of thesema4abreceptorplxnb1a/b, expressed by spinal progenitor cells, also moderately increases regenerative neurogenesis. In addition, single cell transcriptomics reveals altered interactions between macrophages and multiple additional cell types aftersema4abdisruption. Pro-inflammatory cytokines are down-regulated and fibroblasts upregulate expression of the anti-inflammatory cytokinetgfb3.Inhibition oftgfb3abolishes effects ofsema4abdisruption on regenerative neurogenesis. This highlightssema4abas a direct and indirect inhibitor of regenerative neurogenesis and as a potential therapeutic target in non-regenerating mammals.

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PREreview by María Constanza Silvera et al.

Authored by María Constanza Silvera and Daniel Prieto

The paper explores the function of one of the zebrafish orthologs of sema4a, sema4ab, which is highly enriched in macrophages/microglia and signal to spinal progenitors expressing the paralog receptors plxnb1a and plxnb1b after spinal cord injury.
The main finding is the identification of the…

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PREreviews of Macrophage crosstalk with neural progenitors and fibroblasts controls regenerative neurogenesis via Sema4ab after spinal cord injury in zebrafish

1 PREreview