Macrophages modulate adult zebrafish tail fin regeneration

TLDR

In mammals, neutrophils and macrophages are key mediators of inflammation essential for tissue repair, but whether analogous cells are functionally important for wound healing or regeneration in adult zebrafish remains unknown. The study aimed to track neutrophil and macrophage migration after tail fin amputation in adult zebrafish and to identify molecular regulators of inflammation, such as Wnt/β‑catenin. The authors used transgenic zebrafish expressing neutrophil and macrophage markers to track cell migration after fin amputation and employed macrophage‑specific ablation to test their role in regeneration. Macrophages were found to have stage‑dependent roles in fin outgrowth and bony ray patterning by modulating blastema proliferation, and Wnt/β‑catenin signaling was identified as a key regulator of the inflammatory microenvironment and macrophage phenotype, linking inflammation to regeneration.

Abstract

Neutrophils and macrophages, as key mediators of inflammation, have defined functionally important roles in mammalian tissue repair. Although recent evidence suggests that similar cells exist in zebrafish and also migrate to sites of injury in larvae, whether these cells are functionally important for wound healing or regeneration in adult zebrafish is unknown. To begin to address these questions, we first tracked neutrophils (lyzC(+), mpo(+)) and macrophages (mpeg1(+)) in adult zebrafish following amputation of the tail fin, and detailed a migratory timecourse that revealed conserved elements of the inflammatory cell response with mammals. Next, we used transgenic zebrafish in which we could selectively ablate macrophages, which allowed us to investigate whether macrophages were required for tail fin regeneration. We identified stage-dependent functional roles of macrophages in mediating fin tissue outgrowth and bony ray patterning, in part through modulating levels of blastema proliferation. Moreover, we also sought to detail molecular regulators of inflammation in adult zebrafish and identified Wnt/β-catenin as a signaling pathway that regulates the injury microenvironment, inflammatory cell migration and macrophage phenotype. These results provide a cellular and molecular link between components of the inflammation response and regeneration in adult zebrafish.