Spotlight on zebrafish: the next wave of translational research

Patton, E. Elizabeth; Tobin, David M.

doi:10.1242/dmm.039370

Cited by 37 publications

(29 citation statements)

References 38 publications

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“…We argue that the candidate markers from carp could aid the development of new transgenic zebrafish targeting M1 and M2 macrophages 13 . Transgenic zebrafish, well known for the possibility to visualize and follow specific immune cells in vivo 103 , 104 may be of great help tracing M1- and M2-like macrophages in real time.…”

Section: Discussionmentioning

confidence: 99%

Transcriptome sequencing supports a conservation of macrophage polarization in fish

Wentzel

Petit

Veen

et al. 2020

Sci Rep

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Mammalian macrophages can adopt polarization states that, depending on the exact stimuli present in their extracellular environment, can lead to very different functions. Although these different polarization states have been shown primarily for macrophages of humans and mice, it is likely that polarized macrophages with corresponding phenotypes exist across mammals. evidence of functional conservation in macrophages from teleost fish suggests that the same, or at least comparable polarization states should also be present in teleosts. However, corresponding transcriptional profiles of marker genes have not been reported thus far. In this study we confirm that macrophages from common carp can polarize into M1-and M2 phenotypes with conserved functions and corresponding transcriptional profiles compared to mammalian macrophages. Carp M1 macrophages show increased production of nitric oxide and a transcriptional profile with increased pro-inflammatory cytokines and mediators, including il6, il12 and saa. Carp M2 macrophages show increased arginase activity and a transcriptional profile with increased anti-inflammatory mediators, including cyr61, timp2b and tgm2b. our RnA sequencing approach allowed us to list, in an unbiased manner, markers discriminating between M1 and M2 macrophages of teleost fish. We discuss the importance of our findings for the evaluation of immunostimulants for aquaculture and for the identification of gene targets to generate transgenic zebrafish for detailed studies on M1 and M2 macrophages. Above all, we discuss the striking degree of evolutionary conservation of macrophage polarization in a lower vertebrate. Depending on stimuli present in their extracellular environment, mammalian macrophages can adopt polarization states that can exert very different, sometimes opposite, functions. These opposite functional differences were initially referred to as the M1/M2 paradigm 1 , in which M1 macrophages exert pro-inflammatory activities driven by Th1 cytokines as opposed to M2 macrophages that would be driven by Th2 cytokines and be involved in anti-inflammatory responses. This paradigm is primarily based on arginine metabolism, as inflammatory M1 macrophages metabolize arginine to produce anti-microbial nitric oxide (NO) while anti-inflammatory M2 macrophages utilize the same arginine to produce proline and polyamines required for cell proliferation and tissue generation. In more recent studies, the M1/M2 paradigm has been refined to include at least nine distinct macrophage activation states 2 or define M1 and M2 macrophages at the opposite ends of an entire spectrum of activation states 2-5. Different macrophage polarization states have been studied in detail in mice and men, however it remains unclear to what extend these polarized phenotypes are conserved in non-mammalian species. Although considerable differences exist between polarized macrophages of mammals including mice and men 6-8 , their M1 and M2 macrophages display comparable core phenotypes and it is likely that polarized macroph...

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Section: Discussionmentioning

confidence: 99%

Transcriptome sequencing supports a conservation of macrophage polarization in fish

Wentzel

Petit

Veen

et al. 2020

Sci Rep

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“…Although initially used to study embryonic development, the zebrafish has emerged as a versatile animal model in diverse areas of biomedical research, including immunology, toxicology, cancer, and behavioral biology (Tavares and Santos Lopes, 2013 ; Patton and Tobin, 2019 ). In recent years, there have been many successful attempts modeling human diseases using zebrafish.…”

Section: Introductionmentioning

confidence: 99%

Modeling Inflammation in Zebrafish for the Development of Anti-inflammatory Drugs

Xie

Meijer

Schaaf

2021

Front. Cell Dev. Biol.

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Dysregulation of the inflammatory response in humans can lead to various inflammatory diseases, like asthma and rheumatoid arthritis. The innate branch of the immune system, including macrophage and neutrophil functions, plays a critical role in all inflammatory diseases. This part of the immune system is well-conserved between humans and the zebrafish, which has emerged as a powerful animal model for inflammation, because it offers the possibility to image and study inflammatory responses in vivo at the early life stages. This review focuses on different inflammation models established in zebrafish, and how they are being used for the development of novel anti-inflammatory drugs. The most commonly used model is the tail fin amputation model, in which part of the tail fin of a zebrafish larva is clipped. This model has been used to study fundamental aspects of the inflammatory response, like the role of specific signaling pathways, the migration of leukocytes, and the interaction between different immune cells, and has also been used to screen libraries of natural compounds, approved drugs, and well-characterized pathway inhibitors. In other models the inflammation is induced by chemical treatment, such as lipopolysaccharide (LPS), leukotriene B4 (LTB4), and copper, and some chemical-induced models, such as treatment with trinitrobenzene sulfonic acid (TNBS), specifically model inflammation in the gastro-intestinal tract. Two mutant zebrafish lines, carrying a mutation in the hepatocyte growth factor activator inhibitor 1a gene (hai1a) and the cdp-diacylglycerolinositol 3-phosphatidyltransferase (cdipt) gene, show an inflammatory phenotype, and they provide interesting model systems for studying inflammation. These zebrafish inflammation models are often used to study the anti-inflammatory effects of glucocorticoids, to increase our understanding of the mechanism of action of this class of drugs and to develop novel glucocorticoid drugs. In this review, an overview is provided of the available inflammation models in zebrafish, and how they are used to unravel molecular mechanisms underlying the inflammatory response and to screen for novel anti-inflammatory drugs.

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“…With the recent technological advances in precise gene editing, the use of zebrafish in genetic engineering studies has drastically increased in the last five years (Patton and Tobin, 2019;Santoriello and Zon, 2012). The CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)/Cas9 system is indeed a remarkably powerful gene editing tool (Sander and Joung, 2014) that enables the rapid and efficient generation of loss-of-function mutations in this model.…”

Section: Introductionmentioning

confidence: 99%

Precise base editing for thein vivostudy of developmental signaling and human pathologies in zebrafish

Rosello

Vougny

Czarny

et al. 2020

Preprint

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While zebrafish is emerging as a new model system to study human diseases, an efficient methodology to generate precise point mutations at high efficiency is still lacking. Here we show that base editors can generate C-to-T point mutations with high efficiencies without other unwanted on-target mutations. In addition, we established a new editor variant recognizing an NAA PAM, expanding the base editing possibilities in zebrafish. Using these approaches, we first generated a base change in the ctnnb1 gene, mimicking oncogenic mutations of the human gene known to result in constitutive activation of endogenous Wnt signaling. Additionally, we precisely targeted several cancer-associated genes among which cbl. With this last target we created a new zebrafish dwarfism model. Together our findings expand the potential of zebrafish as a model system allowing new approaches for the endogenous modulation of cell signaling pathways and the generation of precise models of human genetic disease associated-mutations.

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Spotlight on zebrafish: the next wave of translational research

Cited by 37 publications

References 38 publications

Transcriptome sequencing supports a conservation of macrophage polarization in fish

Transcriptome sequencing supports a conservation of macrophage polarization in fish

Modeling Inflammation in Zebrafish for the Development of Anti-inflammatory Drugs

Precise base editing for thein vivostudy of developmental signaling and human pathologies in zebrafish

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