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Development (Cambridge, England) Sep 2019Tissue damage can resolve completely through healing and regeneration, or can produce permanent scarring and loss of function. The response to tissue damage varies... (Review)
Review
Tissue damage can resolve completely through healing and regeneration, or can produce permanent scarring and loss of function. The response to tissue damage varies across tissues and between species. Determining the natural mechanisms behind regeneration in model organisms that regenerate well can help us develop strategies for tissue recovery in species with poor regenerative capacity (such as humans). The zebrafish () is one of the most accessible vertebrate models to study regeneration. In this Primer, we highlight the tools available to study regeneration in the zebrafish, provide an overview of the mechanisms underlying regeneration in this system and discuss future perspectives for the field.
Topics: Animals; Drug Evaluation, Preclinical; Genetic Techniques; Humans; Models, Animal; Organogenesis; Regeneration; Zebrafish
PubMed: 31540899
DOI: 10.1242/dev.167692 -
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 -
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 -
Cellular and Molecular Life Sciences :... Dec 2021Zebrafish have emerged as a major model organism to study vertebrate reproduction due to their high fecundity and external development of eggs and embryos. The... (Review)
Review
Zebrafish have emerged as a major model organism to study vertebrate reproduction due to their high fecundity and external development of eggs and embryos. The mechanisms through which zebrafish determine their sex have come under extensive investigation, as they lack a definite sex-determining chromosome and appear to have a highly complex method of sex determination. Single-gene mutagenesis has been employed to isolate the function of genes that determine zebrafish sex and regulate sex-specific differentiation, and to explore the interactions of genes that promote female or male sexual fate. In this review, we focus on recent advances in understanding of the mechanisms, including genetic and environmental factors, governing zebrafish sex development with comparisons to gene functions in other species to highlight conserved and potentially species-specific mechanisms for specifying and maintaining sexual fate.
Topics: Animals; Female; Germ Cells; Male; Protein Processing, Post-Translational; RNA; Sex Determination Processes; Sex Differentiation; Zebrafish
PubMed: 34936027
DOI: 10.1007/s00018-021-04066-4 -
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 -
Developmental Cell Jun 2023The hematopoietic niche is a supportive microenvironment composed of distinct cell types, including specialized vascular endothelial cells that directly interact with...
The hematopoietic niche is a supportive microenvironment composed of distinct cell types, including specialized vascular endothelial cells that directly interact with hematopoietic stem and progenitor cells (HSPCs). The molecular factors that specify niche endothelial cells and orchestrate HSPC homeostasis remain largely unknown. Using multi-dimensional gene expression and chromatin accessibility analyses in zebrafish, we define a conserved gene expression signature and cis-regulatory landscape that are unique to sinusoidal endothelial cells in the HSPC niche. Using enhancer mutagenesis and transcription factor overexpression, we elucidate a transcriptional code that involves members of the Ets, Sox, and nuclear hormone receptor families and is sufficient to induce ectopic niche endothelial cells that associate with mesenchymal stromal cells and support the recruitment, maintenance, and division of HSPCs in vivo. These studies set forth an approach for generating synthetic HSPC niches, in vitro or in vivo, and for effective therapies to modulate the endogenous niche.
Topics: Animals; Stem Cell Niche; Transcription Factors; Endothelial Cells; Zebrafish; Gene Expression Regulation
PubMed: 37119815
DOI: 10.1016/j.devcel.2023.04.007 -
Disease Models & Mechanisms Sep 2019Zebrafish offer a powerful vertebrate model for studies of development and disease. The major advantages of this model include the possibilities of conducting reverse... (Review)
Review
Zebrafish offer a powerful vertebrate model for studies of development and disease. The major advantages of this model include the possibilities of conducting reverse and forward genetic screens and of observing cellular processes by imaging of single cells. Moreover, pathways regulating blood development are highly conserved between zebrafish and mammals, and several discoveries made in fish were later translated to murine and human models. This review and accompanying poster provide an overview of zebrafish hematopoiesis and discuss the existing zebrafish models of blood disorders, such as myeloid and lymphoid malignancies, bone marrow failure syndromes and immunodeficiencies, with a focus on how these models were generated and how they can be applied for translational research.
Topics: Animals; Disease Models, Animal; Drug Evaluation, Preclinical; Hematologic Diseases; Hematopoiesis; Zebrafish
PubMed: 31519693
DOI: 10.1242/dmm.040360 -
Zhongguo Yi Xue Ke Xue Yuan Xue Bao.... Aug 2022Circular RNAs (circRNAs),a group of highly conserved small RNAs,are characterized by a closed circular structure from precursor linear RNA through reverse splicing.They...
Circular RNAs (circRNAs),a group of highly conserved small RNAs,are characterized by a closed circular structure from precursor linear RNA through reverse splicing.They are powerful regulators of the physiological and pathological processes in organisms at different development stages.Zebrafish can be used for the high-throughput drug screening with low cost.Thus,the circRNAs associated with development and inflammation can be mined from zebrafish.Recently,a variety of circRNAs in zebrafish have been identified and characterized.Studies have proved that circRNAs play a vital role in the development and inflammation of zebrafish.The paper summarizes the classification,characteristics,and biological functions of circRNAs,and reviews the research progress in zebrafish's circRNAs.
Topics: Animals; Inflammation; RNA; RNA, Circular; Zebrafish
PubMed: 36065704
DOI: 10.3881/j.issn.1000-503X.13975