In zebrafish larvae the vessels and blood flow can easily be visualized by using simple dissecting microscope and also by using fluorescent proteins; the development of the blood vascular system could be examined in great details. It is a bony fish (teleost) that belongs to the family Cyprinidae under the class Actinopterygii (ray-finned fishes). Very briefly, the origins of a few model organisms are described, including E. coli, yeast, C. elegans, Drosophila, Xenopus, zebrafish, mouse, maize and Arabidopsis. It’s based on principles of collaboration, unobstructed discovery, and, most importantly, scientific progression. Adult zebrafish are small in size, they grow quickly, and they breed readily. Xenotransplantation represents another novel way to induce tumor in zebrafish. About 70% of genes associated with disease in humans have functional homologs in zebrafish [8]. Subsequently, a large variety of creative approaches were used to develop disease models that are used to study developmental disorders, cancer, heart disease, diabetes, and many other conditions. Among different fish species of interest to aquaculture, zebrafish is genetically more tractable. The zebrafish model has recently emerged as a significant experimental system for developmental biology studies. It is only 50 years later after an increased rise of interest for zebrafish as an animal model that George Streisinger began a genetic screen of zebrafish using gamma-rays to cause random mutations in … A variety of fishes have been used as model to study tumors induced by environmental carcinogens. By 72 h, the embryo hatches out from the eggshell and within the next 2 days starts hunting for food. In the late 1960s, George Streisinger, who is considered the founding father of zebrafish research, first introduced this tiny slender fish as a vertebrate model for research on genetics and development at the University of Oregon. She wants to use developmental models that can uncover broader regulatory mechanisms applicable to disease, especially those in which developmental pathways are reactivated, such as in cancer. Like other vertebrates, the zebrafish gastrointestinal tract is a complex organ composed of multiple cell types like epithelial, muscular, vascular, neural, and immune cells. Hypermethylation of tumorigenetic genes has negative impact (regulation) over tumor suppressor genes (TSGs), DNA repair genes, and antiangiogenic genes, and it is a common quality of neoplastic cells [55, 60, 61, 62, 63]. Reprodu… Primarily cancer is a disease of adults, but through mutagenesis screens, cell cycle phenotype could be examined in rapidly developing transparent embryos of the zebrafish. Methylation of DNA at CpG dinucleotides is an important component of epigenetic gene expression regulation [55] that causes the modulation of protein-DNA interactions [56, 57]. The zebrafish model has been exploited recently to recognize the key molecules which are responsible for the development of cutaneous squamous cell carcinoma (cSCC) and head and neck squamous cell carcinoma (HNSCC) [72] as well as for SCC target therapies [79]. The same approach was adopted to compare the development of blood and lymphatic vasculatures in zebrafish [35]. This two-day virtual symposium will explore alchemy’s practical and applied uses and their lasting impact on chemistry, technology, medicine, experimentation, and the marketplace. Aberrant methylation of CpG islands (CGT) takes place in the exonic and promoter regions [58, 59] and changes in gene expression associated with tumorigenesis. 2. The effects of drugs on growth and development can be examined visually through length and shape of the zebrafish body as well as the morphology of internal organs such as the brain, liver, cardiovascular system, pancreas, intestine, kidney, notochord, etc. The invertebrates such as flies and nematodes also can develop anomalies in cell proliferation. Login to your personal dashboard for more detailed statistics on your publications. Uno de los modelos animales más populares de la investigación es el Zebrafish, un pescado tropical que sea nativo a los arroces de arroz de Asia. Among all the zebrafish proved best for investigating embryogenesis, organogenesis, and impact of environmental carcinogen for the development of cancer [64]. As like humans, cancer is a genetic disease in fishes as shown by melanomas which develop in Xiphophorus hybrids [47]. Since young zebrafish are transparent, scientists can now see some of the most crucial life processes as they happen. Studies involving Zebrafish have been important in many fields of research including oncology, regeneration and particularly embryonic development. The lethal concentration (LC50) of different chemicals has been determined in embryos of zebrafish and has been compared with the mammalian LC50, and it has been found that median lethal dose of zebrafish is lower than mammals [84]. These results in zebrafish exhibit similarities with humans [101]. Realizing the importance of zebrafish model, Grunwald and Eisen used this developmental model to study the segmental structure of the brain and characterized neurons in zebrafish for the first time in a vertebrate model [17]. Learn more >>. The zebrafish genome shares a lot of similarities with human genome. By using confocal microscopy and time-lapse imaging, the detailed morphogenetic movements and cell shape changes can be carried out in live specimens [31]. The endothelial cells of the vascular system can be stained by fluorescent dye/protein that helps to visualize the neovascularization of tiny tumor at the earliest stage, and metastasizing tumor cells can be tracked explicitly at cellular level [7]. Nüsslein-Volhard recognized the importance of zebrafish as a vertebrate model to study developmental biology by identifying developmentally important genes [18]. Zebrafish can be used as a model organism not only to detect the concentration of endocrine disruptors in the aquatic environment but also to assess their toxic effects in reproductive and nervous systems. The genes regulating cell cycle, cell proliferation, and apoptosis have already been screened in yeast, Drosophila and C. elegans, in the similar way gene functions for these biological pathways can be screened in zebrafish to understand the events that lead to the development of cancer in any vertebrate species [43]. By inducing different gene mutations or stimulating signaling pathways through chemicals, the tumors can be induced in different organs of the zebrafish like the pancreas, liver, GI tract, vasculature, muscles, skin, and testes [46, 48, 49, 50, 51]. Working to complete a PhD in cell and molecular biology at the University of Pennsylvania, with a focus on developmental, stem-cell, and regenerative biology, Francesca Tuazon is interested in the mechanisms that regulate dynamic signaling events in both time and space. For vascular development and growth, angiogenesis plays a very important role. In this review, we provide an introduction to the zebrafish model system by overviewing set-up and husbandry requirements, the … For drug discovery, zebrafish are especially valuable in the earlier stages of research as they provide a model organism to demonstrate a new treatment's efficacy and toxicity before more costly mammalian models are used. HeadquartersIntechOpen Limited5 Princes Gate Court,London, SW7 2QJ,UNITED KINGDOM. The individual cell growth during vascular development also can be tracked. The zebrafish (Danio rerio) is a freshwater fish belonging to the minnow family (Cyprinidae) of the order Cypriniformes. [85, 86, 87, 88, 89, 90]. The regenerating vessels in the regenerating caudal fin originate from vein-derived cells that have angiogenic potential [41]. The author declares that there is no conflict of interest. The process of drug discovery is divided into four main components: screening of lead compounds, target identification, target validation, and assay development [96]. In a period of just 4 days, the embryo converts rapidly into a small version of adult. They are also very cheap; however, they do require more space than other model organisms such as flies. Angiogenesis is the process through which new blood vessels originate from preexisting vascular structures which play essential role in healthy physiological and pathological conditions. Francesca Tuazon will discuss the history of model organisms and the technological advances afforded by using zebrafish. We share our knowledge and peer-reveiwed research papers with libraries, scientific and engineering societies, and also work with corporate R&D departments and government entities. The rapid development simplifies development and genetic studies. Recently advances have been made to study the development of the enteric nervous system (ENS) using the zebrafish model. The cloning of mutated genes screened for specific phenotypes in zebrafish has similarities in humans and thus serves as model for human disease and to study underlying mechanisms. The zebrafish is acquiring the reputation rapidly as a promising model animal to study drug and chemical toxicology [92, 93]. In drug development, cardiotoxicity is one of the major concerns. because low cost and easy maintenance, transparent embryo, easy manipulation, high fecundity, and rapid embryonic development favor the zebrafish as an attractive model for in vivo assays with simplicity and versatility of in vitro assays over mammalian models which lack all of these benefits. But, there are also purely scientific reasons why ‘lower’ organisms, such as zebrafish, *Address all correspondence to: insectqh11@gmail.com, Edited by Liliana Streba, Dan Ionut Gheonea and Michael Schenker. Several other types of tumor, such as pancreatic cancer, lung cancer, ovarian carcinoma, breast cancer, prostate cancer, retinoblastoma, leukemia, etc., have also been transplanted in the zebrafish [7]. Now, zebrafish has got the status of a successful animal model to study drug toxicity and toxicology caused by environmental contaminants [91]. ... JPS welcomes a panel of industry leaders for a virtual discussion about the development and commercialization of nonanimal foods. Hepatic gene expression in humans and zebrafish has revealed conservation of gene expression profiles at different stages of tumor aggressiveness between these two phylogenetically distant species [66, 67]. The embryo develops very fast, and the blastula stage lasts only for 3 h, while gastrulation gets completed in 5 h; in an embryo that is about 18 h old, very well developed ears, eyes, segmenting muscles, and brain can be viewed as the embryo is transparent. To better understand the process of metastasis, the transplanted tumor cells can be stained/treated by dye like CM-Dil or may be labeled by red fluorescent protein (RFP) [82]. The Joseph Priestley Society welcomes economist Robert Fry, who will present his outlook for the global economy, with an emphasis on U.S. manufacturing and the chemical industry in particular. Here, we review some achievements of zebrafish-based assays for modeling human diseases and for drug discovery and development. Because of many significant disadvantages in the previous studies using in vivo mouse model, the metastasis process cannot be abstracted properly, but zebrafish cancer model has overcome the drawback of previous models and has shown exceptional strengths. Danio rerio (Zebrafish) The Zebrafish is a widely used vertebrate model for development, it was first established as a useful model organism by George Streisinger, Zebrafish are as commonly used as rats and mice. After successive amputations the full regeneration of the caudal fin used to take place within couple of weeks [40]. Vijay Kapur, retired CEO of International Solar Electric Technology, presents this month’s virtual JPS talk. Most of the tissues and organs found in humans and zebrafish are the same except lungs and prostrate and mammary glands. As explored by Verkerk AO and Remme CA. Dear Colleagues, The need of animal models to understand and offer better treatment for human diseases is still indispensable. [94] developed a test in which susceptible zebrafish was used to detect small molecule-induced mutagenesis. The process of target identification involves the recognition of target gene or protein which when modulated by a drug can have positive effects on the progression of disease. Each chapter focuses on a species that is either now a model organism or that was once a promising candidate but ultimately failed to gain long-term acceptance among researchers. 7 8. Melanoma is the most pernicious form of skin cancer among all types of skin cancers and has mortality rate over 80% [71, 72]. Choosing zebrafish for modeling cancer studies has many advantages. BIOGRAPHY Ronald Plasterk, is a Dutch politician of the Labour Party and successful scientist and molecular genetics. Advantages of using Zebrafish as a Model Organism. This has increased concerns associated with potential toxicity of nanoproducts to humans and the environments. Especially oral squamous cell carcinoma (OSCC) accounts for about 24% of HNSCC with a mortality rate of 2 million deaths every year [76, 78]. Treatment with terfenadine and clomipramine caused severe impairment of cardiac functions, edema, hemorrhage, arrested heartbeat, and even death. Cancer is a cursed reality for millions of humans worldwide and in fact for all vertebrates. The vascular system of tumor has always been the target of antitumor therapies; it is evident from research and clinical observations that if angiogenesis inhibitors are used in combination with chemotherapy, it can improve the outcome in cancer patients [69]. The importance of angiogenesis has been discussed well in the previous section on development. The future of zebrafish as model organism is very bright. As discussed previously in Section 1, because of many advantages, the zebrafish has recently emerged as a prominent model for toxicological studies and drug discovery. Available from: Novel Implications of Exosomes in Diagnosis and Treatment of Cancer and Infectious Disease... Use of zebrafish in developmental biology, Zebrafish as a model organism for aquaculture species, Department of Biology, Deanship of Educational Services, Qassim University, Saudi Arabia, Department of Plant Production and Protection, College of Agriculture and Veterinary Medicine, Qassim University, Saudi Arabia. DISTRIBUTION 6 7. Zebrafish model also has been used in the study of angiogenesis and regeneration. The zebrafish recently emerged as a powerful new model organism for biomedical research. Studies in History and Philosophy of … In adults, the caudal fin is equally convenient as a model tissue as regenerating vessels can be observed at all stages, and the animals (zebrafish) are suitable for experimental drug manipulations [31]. Zebrafish embryos are used as predictive model to assess the toxicity in mammals. This talk will also delve into one of life’s biggest mysteries and science’s oldest questions: how do we become what we are? Yes, I do think that the zebrafish will be a model organism for how development of a vertebrate will happen. This provides insight into the genetic control of developmental processes in humans because their genomes are similar. Chemically induced tumors in zebrafish and humans are histopathologically similar [43, 65], and orthologous oncogenes and tumor suppressor genes (TSGs) have been identified in fishes and humans [65]. The embryo develops rapidly outside mother and optically clear and thus, easily accessible for experimentation and observation. In addition to the features of zebrafish mentioned above, it requires very low space and maintenance cost. The embryos of zebrafish were utilized to compare the developmental toxicity resulting from the exposure to ethanol or acetaldehyde [95]. The caudal fin especially provides an ideal tissue for vascular regeneration studies due to its simple and fine architecture and relative transparency [39]. The zebrafish can be used to study melanoma development, progression, drug screening, and treatment. © 2018 The Author(s). Zebrafish was first used as a biological model by George Streisinger (University of Oregon) in the 1970s because it was simpler over mouse and easy to manipulate genetically. Zebrafish in research . Zebrafish (Danio rerio) are small tropical fish (2.5-4 cm long) found natively in south Asia.First used in the 1960s in biological research, Zebrafish have proven to be excellent model organisms for developmental and disease studies. In the beginning of melanoma, it is restricted to the epidermis because of the radial growth phase (RGP) of melanoma, and it can be removed by surgical excision [73]. Zebrafish have been introduced to parts of the United States. Abstract. The drugs that were used to evaluate the organ toxicity were gentamicin, cisplatin, vinblastine, quinine, neomycin, doxorubicin, dexamethasone, cyclosporin A, caffeine, camptothecin, MPA, fluorouracil, etc. Our Saturday Speaker series features a short talk on an intriguing scientific topic, followed by a Q&A or discussion over complimentary tea and coffee. Vascular anatomy development of zebrafish using molecular tracers during early embryonic stages has high level of similarities with other vertebrates [1, 32, 33]. Zebrafish is a successful and versatile animal model system, offering a tool to model gene function, development of various organ systems, cancer studies, toxicology, drug discovery, human disease and disorders and also in aquaculture, etc. by George Streisinger in 1970. The use of Zebrafish as a model organism was pioneered at the University of Oregon,U.S.A. As a fish hobbyist, Streisinger recognized the potential of zebrafish as a vertebrate model of development. Zebrafish are widely used in research due to their numerous beneficial properties. The Science History Institute’s building is currently closed to the public. The adaptive immune system in larvae of zebrafish usually develops after 14 DPF, which provides very conducive environment for survival of transplanted cancer cells and metastasis [81], and the process of tumor metastasis can be observed through the transparent body of zebrafish under microscope. The zebrafish model also has been used to know the organ function assays and assessment of drug effect [84]. He is the “Founder Father” of Zebrafish Developmental and Genetic Research. An example of a beneficial synergistic is that zebrafish can be used to screen relatively quickly, cheaply and with a high resolution for phenotypic changes resulting from specific genetic manipulation. In this chapter author summarizes some of the recent advances in the area of zebrafish research, viz., developmental biology, toxicology, transgenic studies, human disease, drug discovery, cancer, etc. Among the model organisms, the zebrafish (Danio rerio) is one of the best leading models to study developmental biology, cancer, toxicology, drug discovery, and molecular genetics. Many of the critical pathways that control development in vertebrates are highly conserved between human and zebrafish. In RFP treated U87 glioma stem cells (GSCs), when transplanted into the yolk sac of the zebrafish embryo, the various invasive stages of GSCs like approaching, cluster formation, invasion, migration, and transmigration can be observed clearly at 48 h postinjection [83]. The gut of the zebrafish (teleost) and amniotes have structural similarities, but in teleost it is less complex as compared to amniotes [19]. Therefore, we can finally achieve direct monitoring and early warnings of endocrine disruptors with this model organism. Model organisms are not organisms that get dressed up and pose for pictures (although that would be cool). These model organisms were chosen because of their importance and wide use, which made them systems of choice for genome-wide studies. Photograph 01 George Streisinger. Our readership spans scientists, professors, researchers, librarians, and students, as well as business professionals. The angiogenesis has already been discussed earlier in detail in previous sections on development and cancer. Today zebrafish is a well-established model organism in developmental genetics. The zebrafish disease models are being used in various infections of aquaculture, for instance, tuberculosis and streptococcal and salmonella infections [114]. ‘Stages in the Development of a Model Organism as a Platform for Mechanistic Models in Developmental Biology: Zebrafish, 1970–2000’. Zebrafish (Danio rerio) is a prominent model organism in biological researches in recent times. Through the transparent zebrafish embryo, various cardiac functions like heart rate, rhythm, contraction, circulation, etc. Open Access is an initiative that aims to make scientific research freely available to all. [10]. Maintenance Firstly, Zebrafish are very robust and easy to maintain. Farmanur Rahman Khan and Saleh Sulaiman Alhewairini (November 27th 2018). When using animals in research, it is important to minimise animal suffering by using the least sentient organism possible to answer the question at hand. Another group of researchers proposed to use a transgenic model for high-throughput testing of small molecules that modulate the heart rate of the zebrafish embryo [102]. We are a community of more than 103,000 authors and editors from 3,291 institutions spanning 160 countries, including Nobel Prize winners and some of the world’s most-cited researchers. The first human disease identified using zebrafish was a blood disorder involving specific defect in hemoglobin production through ALAS2 mutated gene [103]. [14, 15, 16]. By using zebrafish, the suppressing or promoting factors for metastasis can be identified. In one of the experiments, the injected fluorescent microsphere was detected when lumenization and anastomosis of the vascular network were complete [34]. Melanoma usually develops in the pigmented epidermal cells (melanocytes), which are responsible for the production of melanin. To date our community has made over 100 million downloads. Many other mutants which show phenotypic similarities to human disease have been screened and identified. History of zebrafish Charles Creaser was the first to initiate the use of zebrafish in laboratories in the 1930s. Many biomedical breakthroughs owe their discovery to advances in the tools and methods scientists use, especially model organisms. Since young zebrafish are transparent, scientists can now see some of the most crucial life processes as they happen. This tiny fish is a versatile model organism for many fields of research because of its easy maintenance, breeding, and transparent body during early development. Streisinger’s colleagues especially Chuck Kimmel in his university got much impressed by the idea of using zebrafish embryo more attractive to study the development of nervous system. HISTORY 1. Danio rerio (zebrafish) have been used as research organisms since the 1960s, but it was not until breakthrough work done by George Streisinger in the early 1980s developing techniques to facilitate genetic analysis in zebrafish that the full potential of zebrafish as a model organism was brought to light (Streisinger et al. Tumorigenesis is a multistep process induced by chemical carcinogen [52], with accumulation of both epigenetic aberrations and mutations in regulatory regions of genes and disorder of signaling pathways [53, 54]. The answer is quite simply that zebrafish are an excellent vertebrate model organism and here are some reasons why: Small size and speedy growth: The same traits that make zebrafish popular pets also make them good model organisms. Thus, zebrafish is a suitable model for preliminary screening of molecules which have potential therapeutic or toxic effects. This model is also a vertebrate, which gives it an advantage over other models. At this stage, very limited therapeutic options are available, and melanoma frequently deteriorates and becomes untreatable [73, 74]. Animals as model organisms, the silent sentinels, stand watch over the environmental health of the world. Clinically and pathologically this dreaded disease is present almost exclusively in all vertebrates, from fish to humans. can be assessed directly. When kept under optimal conditions, the zebrafish can lay about 200 eggs per week [9, 10]. The vascular network is helpful to transport oxygen and nutrients to the cells; likewise tumor cells also get the supply of all these materials. It is possible to identify the interacting oncogenes via suppressor and enhancer screens which cause the formation of specific type of tumor. Much of the pioneer works that established zebrafish as a model organism were done by George Streisinger, Charles Kimmel, and their colleagues [13]. The zebrafish recently emerged as a powerful new model organism for biomedical research. The zebrafish as an alternative model for angiogenesis and regeneration studies provides the relevance of in vivo assays with simplicity and versatility of in vitro assays. These include neurological disorders [104], hematological disorder [105, 106], cardiovascular diseases [107], muscle disease [108] and cancers [109, 110], Parkinson’s disease [111], anxiety, and posttraumatic stress disorder [112]. The mammalian tumor cells can be transplanted into the zebrafish, dispensing a novel way to study the interactions between transplanted tumor cell and vasculature of host. The zebrafish as a supplement to other model organisms The zebrafish also has great research value as a supplement to other model organisms. Zebrafish ( Danio rerio) are a small‐bodied tropical, freshwater fish species originally from South Asia. cSCC accounts for the most frequent type of non-melanoma cutaneous cancer and constitutes about 20% of all skin malignancies [75, 76]. Dr Caroline Brennan, from Queen Mary University of London, tells the NC3Rs the top five reasons why zebrafish are her model of choice. Highly conserved cancer pathways can be screened genetically using zebrafish. 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