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.
Highlights
In mammals, distinct cells of the inflammatory response play crucial roles in determining the level of repair of injured organs
Neutrophils and macrophages are differentially recruited during fin regeneration In order to characterize the cellular inflammatory response that occurs during adult caudal fin regeneration in zebrafish, we used transgenic fish to track the two most prominent types of inflammatory cells, namely neutrophils and macrophages
Wnt/β-catenin signaling modulates the recruitment and resolution of inflammatory cells Since Wnt/β-catenin signaling is required for blastema formation and regenerative outgrowth in zebrafish caudal fins (Ito et al, 2007; Kawakami et al, 2006; Poss et al, 2000; Stoick-Cooper et al, 2007a,b), and modulates inflammatory processes including scar formation, fibrosis, wound healing and tissue remodeling in mammals (French et al, 2004; Ren et al, 2013; Koch et al, 2011), we investigated whether there might be a role for Wnt/β-catenin signaling in regulating inflammation during fin regeneration
Summary
Distinct cells of the inflammatory response play crucial roles in determining the level of repair of injured organs. Macrophages, comprising distinct subpopulations of M1 or M2 subtypes, secrete growth factors and cytokines that may attract keratinocytes and fibroblasts to trigger either tissue repair or scar formation (Leibovich and Ross, 1975; Serhan and Savill, 2005; Sica and Mantovani, 2012; Murray and Wynn, 2011). It is evident that modulating inflammation could be a useful therapeutic approach to augment tissue healing.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
