Macrophages modulate adult zebrafish tail fin 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.

Dynamic microRNA-101a and Fosab expression controls zebrafish heart regeneration

“…Modulation of macrophages attenuates regeneration in salamander limb, zebrafish appendage and neonatal heart regeneration (Aurora et al, 2014;Godwin et al, 2013;Petrie et al, 2014). Previous work on miR-101a in the mammalian heart suggests that fosab is enriched in cardiac fibroblasts and not CMs (Pan et al, 2012).…”

A diffusible signal derived from hematopoietic cells supports the survival and proliferation of regenerative cells during zebrafish fin fold regeneration

“…This does not rule out the involvement of other hematopoietic cells and endothelial cells for the survival of regenerative cells, but in accordance with our result, a number of reports have suggested the important relationship between myeloid lineage cells and regeneration. A recent study by Petrie et al (2014) showed that ablation of macrophages during adult fin regeneration reduces blastema cell proliferation and causes abnormal regeneration. Although these studies did not inspect apoptosis during regeneration, the decrease of survival factor could be a cause of the regeneration defects observed in these studies.…”

Insights into sensory hair cell regeneration from the zebrafish lateral line

“…Recruitment of macrophages to the vicinity of apoptotic cells is also observed in vertebrates. In the zebrafish fin, macrophages are recruited to the amputation site and required for proliferation in the early stages of tissue outgrowth by activating Wnt signaling [75]. Similarly, macrophages are recruited to injured mouse and chick cochlea and utricle and produce TNFa to promote cell proliferation [76][77][78].…”