-
Current Topics in Developmental Biology 2017As manufacturing processes and development of new synthetic compounds increase to keep pace with the expanding global demand, environmental health, and the effects of... (Review)
Review
As manufacturing processes and development of new synthetic compounds increase to keep pace with the expanding global demand, environmental health, and the effects of toxicant exposure are emerging as critical public health concerns. Additionally, chemicals that naturally occur in the environment, such as metals, have profound effects on human and animal health. Many of these compounds are in the news: lead, arsenic, and endocrine disruptors such as bisphenol A have all been widely publicized as causing disease or damage to humans and wildlife in recent years. Despite the widespread appreciation that environmental toxins can be harmful, there is limited understanding of how many toxins cause disease. Zebrafish are at the forefront of toxicology research; this system has been widely used as a tool to detect toxins in water samples and to investigate the mechanisms of action of environmental toxins and their related diseases. The benefits of zebrafish for studying vertebrate development are equally useful for studying teratogens. Here, we review how zebrafish are being used both to detect the presence of some toxins as well as to identify how environmental exposures affect human health and disease. We focus on areas where zebrafish have been most effectively used in ecotoxicology and in environmental health, including investigation of exposures to endocrine disruptors, industrial waste byproducts, and arsenic.
Topics: Animals; Environmental Health; High-Throughput Screening Assays; Humans; Social Control, Formal; Toxicology; Water Pollution; Zebrafish
PubMed: 28335863
DOI: 10.1016/bs.ctdb.2016.10.007 -
Wiley Interdisciplinary Reviews.... May 2018Hematopoiesis is a complex process with a variety of different signaling pathways influencing every step of blood cell formation from the earliest precursors to final... (Review)
Review
Hematopoiesis is a complex process with a variety of different signaling pathways influencing every step of blood cell formation from the earliest precursors to final differentiated blood cell types. Formation of blood cells is crucial for survival. Blood cells carry oxygen, promote organ development and protect organs in different pathological conditions. Hematopoietic stem and progenitor cells (HSPCs) are responsible for generating all adult differentiated blood cells. Defects in HSPCs or their downstream lineages can lead to anemia and other hematological disorders including leukemia. The zebrafish has recently emerged as a powerful vertebrate model system to study hematopoiesis. The developmental processes and molecular mechanisms involved in zebrafish hematopoiesis are conserved with higher vertebrates, and the genetic and experimental accessibility of the fish and the optical transparency of its embryos and larvae make it ideal for in vivo analysis of hematopoietic development. Defects in zebrafish hematopoiesis reliably phenocopy human blood disorders, making it a highly attractive model system to screen small molecules to design therapeutic strategies. In this review, we summarize the key developmental processes and molecular mechanisms of zebrafish hematopoiesis. We also discuss recent findings highlighting the strengths of zebrafish as a model system for drug discovery against hematopoietic disorders. This article is categorized under: Adult Stem Cells, Tissue Renewal, and Regeneration > Stem Cell Differentiation and Reversion Vertebrate Organogenesis > Musculoskeletal and Vascular Nervous System Development > Vertebrates: Regional Development Comparative Development and Evolution > Organ System Comparisons Between Species.
Topics: Animals; Disease Models, Animal; Hematologic Diseases; Hematopoiesis; Leukemia; Zebrafish
PubMed: 29436122
DOI: 10.1002/wdev.312 -
Pediatric Nephrology (Berlin, Germany) May 2019Kidney disease is a global problem with around three million people diagnosed in the UK alone and the incidence is rising. Research is critical to develop better... (Review)
Review
Kidney disease is a global problem with around three million people diagnosed in the UK alone and the incidence is rising. Research is critical to develop better treatments. Animal models can help to better understand the pathophysiology behind the various kidney diseases and to screen for therapeutic compounds, but the use especially of mammalian models should be minimised in the interest of animal welfare. Zebrafish are increasingly used, as they are genetically tractable and have a basic renal anatomy comparable to mammalian kidneys with glomerular filtration and tubular filtration processing. Here, we discuss how zebrafish have advanced the study of nephrology and the mechanisms underlying kidney disease.
Topics: Animals; Disease Models, Animal; Glomerular Filtration Rate; Humans; Kidney; Kidney Diseases; Regeneration; Zebrafish
PubMed: 29502161
DOI: 10.1007/s00467-018-3921-7 -
Cold Spring Harbor Perspectives in... Aug 2020Metastasis, the dispersal of cancer cells from a primary tumor to secondary sites within the body, is the leading cause of cancer-related death. Animal models have been... (Review)
Review
Metastasis, the dispersal of cancer cells from a primary tumor to secondary sites within the body, is the leading cause of cancer-related death. Animal models have been an indispensable tool to investigate the complex interactions between the cancer cells and the tumor microenvironment during the metastatic cascade. The zebrafish () has emerged as a powerful vertebrate model for studying metastatic events in vivo. The zebrafish has many attributes including ex-utero development, which facilitates embryonic manipulation, as well as optically transparent tissues, which enables in vivo imaging of fluorescently labeled cells in real time. Here, we summarize the techniques which have been used to study cancer biology and metastasis in the zebrafish model organism, including genetic manipulation and transgenesis, cell transplantation, live imaging, and high-throughput compound screening. Finally, we discuss studies using the zebrafish, which have complemented and benefited metastasis research.
Topics: Animals; Disease Models, Animal; Gene Expression Regulation, Neoplastic; Humans; Neoplasm Metastasis; Neoplasms; Tumor Microenvironment; Zebrafish
PubMed: 31615862
DOI: 10.1101/cshperspect.a037077 -
Nature Reviews. Cancer May 2020In precision oncology, two major strategies are being pursued for predicting clinically relevant tumour behaviours, such as treatment response and emergence of drug... (Review)
Review
In precision oncology, two major strategies are being pursued for predicting clinically relevant tumour behaviours, such as treatment response and emergence of drug resistance: inference based on genomic, transcriptomic, epigenomic and/or proteomic analysis of patient samples, and phenotypic assays in personalized cancer avatars. The latter approach has historically relied on in vivo mouse xenografts and in vitro organoids or 2D cell cultures. Recent progress in rapid combinatorial genetic modelling, the development of a genetically immunocompromised strain for xenotransplantation of human patient samples in adult zebrafish and the first clinical trial using xenotransplantation in zebrafish larvae for phenotypic testing of drug response bring this tiny vertebrate to the forefront of the precision medicine arena. In this Review, we discuss advances in transgenic and transplantation-based zebrafish cancer avatars, and how these models compare with and complement mouse xenografts and human organoids. We also outline the unique opportunities that these different models present for prediction studies and current challenges they face for future clinical deployment.
Topics: Animals; Antineoplastic Agents; Disease Models, Animal; Humans; Neoplasms; Precision Medicine; Xenograft Model Antitumor Assays; Zebrafish
PubMed: 32251397
DOI: 10.1038/s41568-020-0252-3 -
Gastroenterology Nov 2015As the incidence of hepatobiliary diseases increases, we must improve our understanding of the molecular, cellular, and physiological factors that contribute to the... (Review)
Review
As the incidence of hepatobiliary diseases increases, we must improve our understanding of the molecular, cellular, and physiological factors that contribute to the pathogenesis of liver disease. Animal models help us identify disease mechanisms that might be targeted therapeutically. Zebrafish (Danio rerio) have traditionally been used to study embryonic development but are also important to the study of liver disease. Zebrafish embryos develop rapidly; all of their digestive organs are mature in larvae by 5 days of age. At this stage, they can develop hepatobiliary diseases caused by developmental defects or toxin- or ethanol-induced injury and manifest premalignant changes within weeks. Zebrafish are similar to humans in hepatic cellular composition, function, signaling, and response to injury as well as the cellular processes that mediate liver diseases. Genes are highly conserved between humans and zebrafish, making them a useful system to study the basic mechanisms of liver disease. We can perform genetic screens to identify novel genes involved in specific disease processes and chemical screens to identify pathways and compounds that act on specific processes. We review how studies of zebrafish have advanced our understanding of inherited and acquired liver diseases as well as liver cancer and regeneration.
Topics: Animals; Disease Models, Animal; Humans; Liver; Liver Diseases; Zebrafish
PubMed: 26319012
DOI: 10.1053/j.gastro.2015.08.034 -
Journal of Orthopaedic Research :... May 2020Advances in next-generation sequencing have transformed our ability to identify genetic variants associated with clinical disorders of the musculoskeletal system.... (Review)
Review
Advances in next-generation sequencing have transformed our ability to identify genetic variants associated with clinical disorders of the musculoskeletal system. However, the means to functionally validate and analyze the physiological repercussions of genetic variation have lagged behind the rate of genetic discovery. The zebrafish provides an efficient model to leverage genetic analysis in an in vivo context. Its utility for orthopedic research is becoming evident in regard to both candidate gene validation as well as therapeutic discovery in tissues such as bone, tendon, muscle, and cartilage. With the development of new genetic and analytical tools to better assay aspects of skeletal tissue morphology, mineralization, composition, and biomechanics, researchers are emboldened to systematically approach how the skeleton develops and to identify the root causes, and potential treatments, of skeletal disease. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:925-936, 2020.
Topics: Animals; Models, Animal; Musculoskeletal Development; Zebrafish
PubMed: 31773769
DOI: 10.1002/jor.24539 -
International Journal of Molecular... Jun 2022To discover new molecules or review the biological activity and toxicity of therapeutic substances, drug development, and research relies on robust biological systems to... (Review)
Review
To discover new molecules or review the biological activity and toxicity of therapeutic substances, drug development, and research relies on robust biological systems to obtain reliable results. Phenotype-based screenings can transpose the organism's compensatory pathways by adopting multi-target strategies for treating complex diseases, and zebrafish emerged as an important model for biomedical research and drug screenings. Zebrafish's clear correlation between neuro-anatomical and physiological features and behavior is very similar to that verified in mammals, enabling the construction of reliable and relevant experimental models for neurological disorders research. Zebrafish presents highly conserved physiological pathways that are found in higher vertebrates, including mammals, along with a robust behavioral repertoire. Moreover, it is very sensitive to pharmacological/environmental manipulations, and these behavioral phenotypes are detected in both larvae and adults. These advantages align with the 3Rs concept and qualify the zebrafish as a powerful tool for drug screenings and pre-clinical trials. This review highlights important behavioral domains studied in zebrafish larvae and their neurotransmitter systems and summarizes currently used techniques to evaluate and quantify zebrafish larvae behavior in laboratory studies.
Topics: Animals; Behavior, Animal; Drug Evaluation, Preclinical; Larva; Mammals; Neurotransmitter Agents; Phenotype; Zebrafish
PubMed: 35743088
DOI: 10.3390/ijms23126647 -
Toxicological Sciences : An Official... May 2018The laboratory zebrafish (Danio rerio) is now an accepted model in toxicologic research. The zebrafish model fills a niche between in vitro models and mammalian... (Review)
Review
The laboratory zebrafish (Danio rerio) is now an accepted model in toxicologic research. The zebrafish model fills a niche between in vitro models and mammalian biomedical models. The developmental characteristics of the small fish are strategically being used by scientists to study topics ranging from high-throughput toxicity screens to toxicity in multi- and transgenerational studies. High-throughput technology has increased the utility of zebrafish embryonic toxicity assays in screening of chemicals and drugs for toxicity or effect. Additionally, advances in behavioral characterization and experimental methodology allow for observation of recognizable phenotypic changes after xenobiotic exposure. Future directions in zebrafish research are predicted to take advantage of CRISPR-Cas9 genome editing methods in creating models of disease and interrogating mechanisms of action with fluorescent reporters or tagged proteins. Zebrafish can also model developmental origins of health and disease and multi- and transgenerational toxicity. The zebrafish has many advantages as a toxicologic model and new methodologies and areas of study continue to expand the usefulness and application of the zebrafish.
Topics: Animals; Behavior, Animal; Embryo, Nonmammalian; Embryonic Development; High-Throughput Screening Assays; Larva; Models, Animal; Toxicology; Xenobiotics; Zebrafish
PubMed: 29471431
DOI: 10.1093/toxsci/kfy044 -
Science (New York, N.Y.) Sep 2021CRISPR-Cas9 can be scaled up for large-scale screens in cultured cells, but CRISPR screens in animals have been challenging because generating, validating, and keeping...
CRISPR-Cas9 can be scaled up for large-scale screens in cultured cells, but CRISPR screens in animals have been challenging because generating, validating, and keeping track of large numbers of mutant animals is prohibitive. Here, we introduce Multiplexed Intermixed CRISPR Droplets (MIC-Drop), a platform combining droplet microfluidics, single-needle en masse CRISPR ribonucleoprotein injections, and DNA barcoding to enable large-scale functional genetic screens in zebrafish. The platform can efficiently identify genes responsible for morphological or behavioral phenotypes. In one application, we showed that MIC-Drop could identify small-molecule targets. Furthermore, in a MIC-Drop screen of 188 poorly characterized genes, we discovered several genes important for cardiac development and function. With the potential to scale to thousands of genes, MIC-Drop enables genome-scale reverse genetic screens in model organisms.
Topics: Animals; CRISPR-Cas Systems; Cardiovascular System; Cell Culture Techniques; Genetic Testing; High-Throughput Nucleotide Sequencing; Microfluidic Analytical Techniques; Zebrafish
PubMed: 34413171
DOI: 10.1126/science.abi8870