It has been demonstrated well that toxic effects of ten cardiotoxic agents in zebrafish embryos have similar impact as in humans [100]. Tel-Aviv University, Tel Aviv, Israel ABSTRACT The zebrafish has become a model of choice in fundamental and applied life sciences and is widely used in various fields of biomedical research as a human disease model for cancer, metabolic and neurodegenerative diseases, and regenerative medicine.The tr ansparency of the ze - Mammalian tumor cells treated with red fluorescent protein when injected into transgenic zebrafish, the process of tumor cell metastasis and angiogenesis can be viewed well after 48 h of transplantation [83]. The use of Zebrafish as a model organism was pioneered at the University of Oregon,U.S.A. Under laboratory conditions the zebrafish can spawn throughout the year that ensures the constant supply of offspring from designated pairs that makes this transparent fish a quintessential choice for large-scale genetic approaches to identify novel genes and to discover their specific functions in vertebrates [11]. 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. 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 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]. Many of the critical pathways that control development in vertebrates are highly conserved between human and zebrafish. Fishes are exposed to many waterborne carcinogens in the wild that lead to the development of a variety of benign and malignant tumors in teleosts, and these tumors have similar histology as in humans [45, 46]. Zebrafish in research . It is achieved through interaction between endothelial cells and their niche. The gut of the zebrafish (teleost) and amniotes have structural similarities, but in teleost it is less complex as compared to amniotes [19]. Being a transparent vertebrate, the zebrafish has emerged as a convenient alternative to study the early development of the cardiovascular system and observe the flow of blood [31]. The Science History Institute’s building is currently closed to the public. 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. 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. Because of the variety of benefits to use zebrafish as a model organism which are mentioned in “Introduction,” the zebrafish is adroitly exploited to carcinogenic treatment, transplantation of mammalian tumor cells, and transgenic regulations [44]. 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. The gut epithelium of zebrafish is simpler than that of amniotes; it lacks crypts and is arranged in an irregular broad fold rather than forming villi [21, 22]. 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 invertebrates such as flies and nematodes also can develop anomalies in cell proliferation. Through the transparent zebrafish embryo, various cardiac functions like heart rate, rhythm, contraction, circulation, etc. 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. About 70% of genes associated with disease in humans have functional homologs in zebrafish [8]. 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 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. He is the “Founder Father” of Zebrafish Developmental and Genetic Research. 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]. Much of the pioneer works that established zebrafish as a model organism were done by George Streisinger, Charles Kimmel, and their colleagues [13]. The importance of angiogenesis has been discussed well in the previous section on development. These features make this fish an attractive model organism for developmental, toxicological, and transgenic studies [12]. The future of zebrafish as model organism is very bright. By using zebrafish, the suppressing or promoting factors for metastasis can be identified. In addition, the zebrafish is increasingly used as a genetic model organism for aquaculture species and in toxicogenomics and also to generate zebrafish disease models for application in human biomedicines. Metastatic SCCs are responsible for majority of deaths due to non-melanoma skin cancer [70]. cSCC accounts for the most frequent type of non-melanoma cutaneous cancer and constitutes about 20% of all skin malignancies [75, 76]. 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 … ‘Stages in the Development of a Model Organism as a Platform for Mechanistic Models in Developmental Biology: Zebrafish, 1970–2000’. 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. The zebrafish model has recently emerged as a significant experimental system for developmental biology studies. Dr Caroline Brennan, from Queen Mary University of London, tells the NC3Rs the top five reasons why zebrafish are her model of choice. Model organisms are not organisms that get dressed up and pose for pictures (although that would be cool). Studying most questions in humans is neither practical nor feasible, which is why using such model organisms as the zebrafish is vital to discovery—and has been for hundreds of years. Enteric neural crest cell (ENCC) migration along the gut in zebrafish is also similar with that in amniotes. 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. Adult zebrafish are small in size, they grow quickly, and they breed readily. 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]. Built by scientists, for scientists. Not surprisingly, Endersby pays considerable attention to familiar research organisms such as fruit flies, guinea pigs, corn, bacteriophages, and zebrafish. 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 identification of mutants is one of the most important strategies for the study in various areas of biology. Learn more >>. Xenotransplantation represents another novel way to induce tumor in zebrafish. As PhD students, we found it difficult to access the research we needed, so we decided to create a new Open Access publisher that levels the playing field for scientists across the world. ZebrafishasanExperimental Organism Corinne Houart,King’s College, London, UK The zebrafish became, in the last decade, a model organism of choice to study vertebrate development. The zebrafish recently emerged as a powerful new model organism for biomedical research. The evaluation of toxicity of drug is very essential to know the end points of toxicity, dose-response relationships, and mechanism of toxicity and also to determine the toxicodynamics of the drug [91]. Zebrafish are widely used in research due to their numerous beneficial properties. For better therapeutic practices like development of antitumor drugs and advancements of clinical treatments, the insight into mechanism of tumor metastasis is very helpful. Zebrafish model also has been used in the study of angiogenesis and regeneration. The ease of care, year‐round prolific breeding, and transparent, external development have made these fish a popular model vertebrate for many fields of biology. 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. By Jin Wang, Xuan Zhang, Chunxia Ji, Lei Zhang, Yang Di, Wenhui Lou, Xiaoyan Zhang and Jianqing Xu. As explored by Verkerk AO and Remme CA. 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]. Since they are naturally found in ponds, their ideal conditions can be easily replicated. This model is also a vertebrate, which gives it an advantage over other models. The zebrafish genome shares a lot of similarities with human genome. By making research easy to access, and puts the academic needs of the researchers before the business interests of publishers. This talk will also delve into one of life’s biggest mysteries and science’s oldest questions: how do we become what we are? Francesca Tuazon will discuss the history of model organisms and the technological advances afforded by using zebrafish. 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]. ... JPS welcomes a panel of industry leaders for a virtual discussion about the development and commercialization of nonanimal foods. Admission is free, and no reservations are necessary. SCCs are curable in situ by surgical excision. by George Streisinger in 1970. The first human disease identified using zebrafish was a blood disorder involving specific defect in hemoglobin production through ALAS2 mutated gene [103]. Advantages of using Zebrafish as a Model Organism. Yes, I do think that the zebrafish will be a model organism for how development of a vertebrate will happen. In drug development, the toxicity plays a major role. 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]. History of zebrafish Charles Creaser was the first to initiate the use of zebrafish in laboratories in the 1930s. 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 embryos of zebrafish were utilized to compare the developmental toxicity resulting from the exposure to ethanol or acetaldehyde [95]. 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. Skin or dermal cancers represent the most common type of cutaneous malignancy globally, which includes melanoma and carcinoma of squamous cells [70]. Many other mutants which show phenotypic similarities to human disease have been screened and identified. Vijay Kapur, retired CEO of International Solar Electric Technology, presents this month’s virtual JPS talk. All of the steps toward revealing the neuronal basis of behavior summarized in the previous sections become easier if one can simply look to the brain of an animal and see everything that is happening all at once. Especially oral squamous cell carcinoma (OSCC) accounts for about 24% of HNSCC with a mortality rate of 2 million deaths every year [76, 78]. Zebrafish (Danio rerio) as a Model Organism, Current Trends in Cancer Management, Liliana Streba, Dan Ionut Gheonea and Michael Schenker, IntechOpen, DOI: 10.5772/intechopen.81517. Nüsslein-Volhard recognized the importance of zebrafish as a vertebrate model to study developmental biology by identifying developmentally important genes [18]. 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. 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. Like that of all vertebrates, the enteric nervous system of zebrafish is also derived from neural crest [24], but it differs potentially from amniotes wherein the enteric nervous system is derived from both the vagal and sacral crests, while in the case of zebrafish, it is derived from the vagal crest only [25, 26, 27, 28]. Very briefly, the origins of a few model organisms are described, including E. coli, yeast, C. elegans, Drosophila, Xenopus, zebrafish, mouse, maize and Arabidopsis. Head and neck squamous cell carcinoma (HNSCC) develops in various places such as the oropharynx and laryngopharynx which is very common worldwide [77]. 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 drug development, cardiotoxicity is one of the major concerns. Many biomedical breakthroughs owe their discovery to advances in the tools and methods scientists use, especially model organisms. HeadquartersIntechOpen Limited5 Princes Gate Court,London, SW7 2QJ,UNITED KINGDOM. Among all the zebrafish proved best for investigating embryogenesis, organogenesis, and impact of environmental carcinogen for the development of cancer [64]. Photograph 01 George Streisinger. The team of these researchers studied the embryonic axis, cell lineage analysis, embryonic formation, development of central and peripheral nervous systems, muscle development, differential regulation of gene expression, etc. Since young zebrafish are transparent, scientists can now see some of the most crucial life processes as they happen. [10]. This provides insight into the genetic control of developmental processes in humans because their genomes are similar. 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. © 2018 The Author(s). 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 same approach was adopted to compare the development of blood and lymphatic vasculatures in zebrafish [35]. The zebrafish model also has been used to know the organ function assays and assessment of drug effect [84]. Here, we review some achievements of zebrafish-based assays for modeling human diseases and for drug discovery and development. 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. The angiogenesis has already been discussed earlier in detail in previous sections on development and cancer. The zebrafish GI tract has no distinct stomach but an enlarged area of the anterior intestine that is known as the intestinal bulb. Depending on conditions, the lifespan of zebrafish ranges from 3 to 5 years. After identification of possible target, the validation process of target begins through determination of protein function and assessment of the druggability of the target [84, 97, 98, 99]. The zebrafish is acquiring the reputation rapidly as a promising model animal to study drug and chemical toxicology [92, 93]. The adult zebrafish attains sexual maturity very quickly, having generation time of about 10 weeks, and also this tiny fish has good fecundity rate. Toxicity of antirheumatic drug like diclofenac was evaluated by using zebrafish. In the 1970s, George Streisinger pioneered the establishment of 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 final organization of the zebrafish ENS is also very simple as compared to that of amniotes; it is composed of single neuron or small group of neurons rather than more complex ganglionated myenteric and submucosal plexuses [27, 29]. In one of the experiments, the injected fluorescent microsphere was detected when lumenization and anastomosis of the vascular network were complete [34]. By 72 h, the embryo hatches out from the eggshell and within the next 2 days starts hunting for food. -- The zebrafish (Danio rerio) is perhaps the model organism with the fastest rising popularity in science right now. The use of zebrafish as a model organism got impetus from the 1990s when it was used to develop two large genetic mutants, one by Nobel Prize winner Christiane Nusslein-Volhard in Tubingen, Germany, and the other by Wolfgang Driever and Mark Fishman in Boston, USA. The zebrafish as a supplement to other model organisms The zebrafish also has great research value as a supplement to other model organisms. These are non-human animal species which can be used to understand specific biological processes and to obtain informations which can provide an insight into working of other organisms. Model organisms are a tool for scientists to better understand biology. Studies in History and Philosophy of … Therefore, we can finally achieve direct monitoring and early warnings of endocrine disruptors with this model organism. Licensee IntechOpen. In a period of just 4 days, the embryo converts rapidly into a small version of adult. In coming years, an increased number of reports are expected on the application of zebrafish as an effective bioindicator. Studies involving Zebrafish have been important in many fields of research including oncology, regeneration and particularly embryonic development. The zebrafish (Danio rerio) is a freshwater fish belonging to the minnow family (Cyprinidae) of the order Cypriniformes. 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. The zebrafish model has been used to see the development of various systems/processes as follows. Being a vertebrate the zebrafish is an ideal model to study cancer, though humans and fishes are separated from their common ancestry but biology of the cancer in both groups of organisms is the same [43]. This chapter is distributed under the terms of the Creative Commons Attribution 3.0 License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Zebrafish have been introduced to parts of the United States. The use of zebrafish as a model organism got impetus from the 1990s when it was used to develop two large genetic mutants, one by Nobel Prize winner Christiane Nusslein-Volhard in Tubingen, Germany, and the other by Wolfgang Driever and Mark Fishman in Boston, USA. The rapid development simplifies development and genetic studies. It takes place in two parallel chains along the length of the developing gut [25, 27, 28]. It is possible to identify the interacting oncogenes via suppressor and enhancer screens which cause the formation of specific type of tumor. The impact of various proangiogenic compounds like simvastatine or penicillamine20 or antiangiogenic compounds like vandetanib or PTK787 can be assessed well and visualized through the development of the vascular system in transparent zebrafish embryo [84]. By Farmanur Rahman Khan and Saleh Sulaiman Alhewairini, Submitted: May 9th 2018Reviewed: September 14th 2018Published: November 27th 2018, Home > Books > Current Trends in Cancer Management. 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. Cutaneous squamous cell carcinoma (cSCC) mostly develops due to UV radiation exposure of epidermal cells, namely, keratinocytes, in which uncontrolled proliferation starts [75]. Maintenance Firstly, Zebrafish are very robust and easy to maintain. These cells migrate individually or in groups and assemble into the vessel in response to chemokine signaling [42]. 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. Publishing on IntechOpen allows authors to earn citations and find new collaborators, meaning more people see your work not only from your own field of study, but from other related fields too. The individual cell growth during vascular development also can be tracked. Also 70% of human disease genes have functional similarities with those of zebrafish [8]. These results in zebrafish exhibit similarities with humans [101]. Contact our London head office or media team here. 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. Brief introduction to this section that descibes Open Access especially from an IntechOpen perspective, Want to get in touch? The process of drug discovery is divided into four main components: screening of lead compounds, target identification, target validation, and assay development [96]. By 24 h, segmentation gets completed, and most primary organ systems are formed. This review is by no means a comprehensive one but an attempt to provide a flavor to the readers some recent advances about this wonderful creature to use in potential researches. The historical development of zebrafish as a model organism can be understood as passing through three stages, which seem to be distinguishable in a similar manner in the histories of many other … Because of this reason, the development and the capability of the formation of blood vessels within the tumor determine the malignancy of the cancer as well as influence the therapeutic effects and prognosis. Farmanur Rahman Khan and Saleh Sulaiman Alhewairini (November 27th 2018). To date our community has made over 100 million downloads. Depending on conditions, the lifespan of zebrafish ranges from 3 to 5 years. In this review, we provide an introduction to the zebrafish model system by overviewing set-up and husbandry requirements, the … Zebrafish has a lot of physiological and genetic similarities with humans, including the brain, digestive tract, musculature, vasculature, and innate immune system [1, 2, 3, 4, 5, 6, 7]. It has been reported that mammalian malignant cells can be xenotransplanted into zebrafish embryos, and they can form tumors [37], and thus models for tumor angiogenesis have been developed [38]. 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. Choosing zebrafish for modeling cancer studies has many advantages. 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. Due to the toxicity problem, many new drugs have been declined by the FDA. Thus, zebrafish is a suitable model for preliminary screening of molecules which have potential therapeutic or toxic effects. Melanoma usually develops in the pigmented epidermal cells (melanocytes), which are responsible for the production of melanin. Angiogenesis is the process through which new blood vessels originate from preexisting vascular structures which play essential role in healthy physiological and pathological conditions. The drugs which affect the physiology of the fishes can be tested easily in zebrafish especially their effect on a range of alleles to assess their genetic property [113]. 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. 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. During embryonic development, the intersegmental vessels are formed by angiogenic sprouting from the dorsal aorta, and they have been the target of studies using genetic perturbations or drugs [36]. 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]. Over the environmental health of the most crucial life processes as they happen correspondence:... 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