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ELife Mar 2015Over the last two decades, the zebrafish has joined the ranks of premier model organisms for biomedical research, with a full suite of tools and genomic resources. Yet... (Review)
Review
Over the last two decades, the zebrafish has joined the ranks of premier model organisms for biomedical research, with a full suite of tools and genomic resources. Yet we still know comparatively little about its natural history. Here I review what is known about the natural history of the zebrafish, where significant gaps in our knowledge remain, and how a fuller appreciation of this organism's ecology and behavior, population genetics, and phylogeny can inform a variety of research endeavors.
Topics: Animals; Bangladesh; Ecology; Ecosystem; Genetic Variation; Geography; India; Nepal; Phylogeny; Zebrafish
PubMed: 25807087
DOI: 10.7554/eLife.05635 -
Methods in Cell Biology 2011The enteric nervous system (ENS) is composed of neurons and glia that modulate many aspects of intestinal function. The ability to use both forward and reverse genetic... (Review)
Review
The enteric nervous system (ENS) is composed of neurons and glia that modulate many aspects of intestinal function. The ability to use both forward and reverse genetic approaches and to visualize development in living embryos and larvae has made zebrafish an attractive model in which to study mechanisms underlying ENS development. In this chapter, we review the recent work describing the development and organization of the zebrafish ENS and how this relates to intestinal motility. We also discuss the cellular, molecular, and genetic mechanisms that have been revealed by these studies and how they are providing new insights into human ENS diseases.
Topics: Animals; Enteric Nervous System; Gastrointestinal Motility; Humans; Zebrafish
PubMed: 21550442
DOI: 10.1016/B978-0-12-387036-0.00006-2 -
Proceedings of the National Academy of... Mar 2020Self-organized pattern behavior is ubiquitous throughout nature, from fish schooling to collective cell dynamics during organism development. Qualitatively these...
Self-organized pattern behavior is ubiquitous throughout nature, from fish schooling to collective cell dynamics during organism development. Qualitatively these patterns display impressive consistency, yet variability inevitably exists within pattern-forming systems on both microscopic and macroscopic scales. Quantifying variability and measuring pattern features can inform the underlying agent interactions and allow for predictive analyses. Nevertheless, current methods for analyzing patterns that arise from collective behavior capture only macroscopic features or rely on either manual inspection or smoothing algorithms that lose the underlying agent-based nature of the data. Here we introduce methods based on topological data analysis and interpretable machine learning for quantifying both agent-level features and global pattern attributes on a large scale. Because the zebrafish is a model organism for skin pattern formation, we focus specifically on analyzing its skin patterns as a means of illustrating our approach. Using a recent agent-based model, we simulate thousands of wild-type and mutant zebrafish patterns and apply our methodology to better understand pattern variability in zebrafish. Our methodology is able to quantify the differential impact of stochasticity in cell interactions on wild-type and mutant patterns, and we use our methods to predict stripe and spot statistics as a function of varying cellular communication. Our work provides an approach to automatically quantifying biological patterns and analyzing agent-based dynamics so that we can now answer critical questions in pattern formation at a much larger scale.
Topics: Algorithms; Animals; Body Patterning; Cell Communication; Data Interpretation, Statistical; Machine Learning; Skin; Skin Pigmentation; Zebrafish
PubMed: 32098851
DOI: 10.1073/pnas.1917763117 -
Zebrafish Jun 2021Intestinal neoplasms and preneoplastic lesions are common in zebrafish research facilities. Previous studies have demonstrated that these neoplasms are caused by a...
Intestinal neoplasms and preneoplastic lesions are common in zebrafish research facilities. Previous studies have demonstrated that these neoplasms are caused by a transmissible agent, and two candidate agents have been implicated: a sp. related to and the intestinal parasitic nematode, , and both agents are common in zebrafish facilities. To elucidate the role of these two agents in the occurrence and severity of neoplasia and other intestinal lesions, we conducted two experimental inoculation studies. Exposed fish were examined at various time points over an 8-month period for intestinal histopathologic changes and the burden of and nematodes. Fish exposed to sp. isolated from zebrafish were associated with preneoplastic lesions. Fish exposed to the nematode alone or with the isolate developed severe lesions and neoplasms. Both inflammation and neoplasm scores were associated with an increase in burden. These results support the conclusions that is a strong promoter of intestinal neoplasms in zebrafish and that alone can also cause intestinal lesions and accelerate cancer development in the context of nematode infection.
Topics: Animals; Fish Diseases; Mycoplasma; Mycoplasma Infections; Nematoda; Nematode Infections; Zebrafish
PubMed: 33999743
DOI: 10.1089/zeb.2020.1955 -
Pharmacology & Therapeutics May 2016The zebrafish model is the only available high-throughput vertebrate assessment system, and it is uniquely suited for studies of in vivo cell biology. A sequenced and... (Review)
Review
The zebrafish model is the only available high-throughput vertebrate assessment system, and it is uniquely suited for studies of in vivo cell biology. A sequenced and annotated genome has revealed a large degree of evolutionary conservation in comparison to the human genome. Due to our shared evolutionary history, the anatomical and physiological features of fish are highly homologous to humans, which facilitates studies relevant to human health. In addition, zebrafish provide a very unique vertebrate data stream that allows researchers to anchor hypotheses at the biochemical, genetic, and cellular levels to observations at the structural, functional, and behavioral level in a high-throughput format. In this review, we will draw heavily from toxicological studies to highlight advances in zebrafish high-throughput systems. Breakthroughs in transgenic/reporter lines and methods for genetic manipulation, such as the CRISPR-Cas9 system, will be comprised of reports across diverse disciplines.
Topics: Animals; Animals, Genetically Modified; Gene Expression; High-Throughput Screening Assays; Humans; Models, Animal; Toxicology; Zebrafish
PubMed: 27016469
DOI: 10.1016/j.pharmthera.2016.03.009 -
Developmental Dynamics : An Official... Jun 2007Somites are the most obvious metameric structures in the vertebrate embryo. They are mesodermal segments that form in bilateral pairs flanking the notochord and are... (Review)
Review
Somites are the most obvious metameric structures in the vertebrate embryo. They are mesodermal segments that form in bilateral pairs flanking the notochord and are created sequentially in an anterior to posterior sequence concomitant with the posterior growth of the trunk and tail. Zebrafish somitogenesis is regulated by a clock that causes cells in the presomitic mesoderm (PSM) to undergo cyclical activation and repression of several notch pathway genes. Coordinated oscillation among neighboring cells manifests as stripes of gene expression that pass through the cells of the PSM in a posterior to anterior direction. As axial growth continually adds new cells to the posterior tail bud, cells of the PSM become relatively less posterior. This gradual assumption of a more anterior position occurs over developmental time and constitutes part of a maturation process that governs morphological segmentation in conjunction with the clock. Segment morphogenesis involves a mesenchymal to epithelial transition as prospective border cells at the anterior end of the mesenchymal PSM adopt a polarized, columnar morphology and surround a mesenchymal core of cells. The segmental pattern influences the development of the somite derivatives such as the myotome, and the myotome reciprocates to affect the formation of segment boundaries. While somites appear to be serially homologous, there may be variation in the segmentation mechanism along the body axis. Moreover, whereas the genetic architecture of the zebrafish, mouse, and chick segmentation clocks shares many common elements, there is evidence that the gene networks have undergone independent modification during evolution.
Topics: Animals; Cell Movement; Cell Polarity; Embryo, Nonmammalian; Gene Expression Regulation, Developmental; Humans; Mesoderm; Zebrafish
PubMed: 17486630
DOI: 10.1002/dvdy.21162 -
Current Opinion in Immunology Feb 2010The amenability of the zebrafish to in vivo imaging and genetic analysis has fueled expanded use of this vertebrate model to investigate the molecular and cellular... (Review)
Review
The amenability of the zebrafish to in vivo imaging and genetic analysis has fueled expanded use of this vertebrate model to investigate the molecular and cellular foundations of host-microbe relationships. Study of microbial encounters in zebrafish hosts has concentrated on developing embryonic and larval stages, when the advantages of the zebrafish model are maximized. A comprehensive understanding of these host-microbe interactions requires appreciation of the developmental context into which a microbe is introduced, as well as the effects of that microbial challenge on host ontogeny. In this review, we discuss how in vivo imaging and genetic analysis in zebrafish has advanced our knowledge of host-microbe interactions in the context of a developing vertebrate host. We focus on recent insights into immune cell ontogeny and function, commensal microbial relationships in the intestine, and microbial pathogenesis in zebrafish hosts.
Topics: Animals; Embryo, Nonmammalian; Gene Expression Regulation, Developmental; Host-Pathogen Interactions; Humans; Zebrafish
PubMed: 20153622
DOI: 10.1016/j.coi.2010.01.006 -
International Journal of Molecular... Mar 2020has been a widely used transparent mutant of zebrafish. It possesses a combined loss of reflective iridophores and light-absorbing melanophores, which gives rise to its...
has been a widely used transparent mutant of zebrafish. It possesses a combined loss of reflective iridophores and light-absorbing melanophores, which gives rise to its almost transparent trunk throughout larval and adult stages. Nevertheless, genomic causal mutations of this transparent phenotype are poorly defined. To identify the potential genetic basis of this fascinating morphological phenotype, we constructed genome maps by performing genome sequencing of 28 zebrafish individuals including wild-type AB strain, (), and mutants. A total of 4.3 million high-quality and high-confidence homozygous single nucleotide polymorphisms (SNPs) were detected in the present study. We also identified a 6.0-Mb linkage disequilibrium block specifically in both and that was composed of 39 functional genes, of which the gene was potentially involved in the regulation of iridophore formation and maintenance. This is the first report of high-confidence genomic mutations in the gene of and that potentially leads to defective splicing as one major molecular clue for the iridophore loss. Additionally, comparative transcriptomic analyses of skin tissues from the AB, and groups revealed detailed transcriptional changes of several core genes that may be involved in melanophore and iridophore degeneration. In summary, our updated genome and transcriptome sequencing of the and mutants provides novel genetic clues for the iridophore loss. These new genomic variation maps will offer a solid genetic basis for expanding the zebrafish mutant database and in-depth investigation into pigmentation of animals.
Topics: Animals; Chromosome Mapping; Female; Genome; Linkage Disequilibrium; Male; Mutation; Pigmentation; Polymorphism, Single Nucleotide; Transcriptome; Zebrafish; Zebrafish Proteins
PubMed: 32235607
DOI: 10.3390/ijms21072385 -
ELife Jun 2022The ability to regulate gene activity spatially and temporally is essential to investigate cell-type-specific gene function during development and in postembryonic...
The ability to regulate gene activity spatially and temporally is essential to investigate cell-type-specific gene function during development and in postembryonic processes and disease models. The Cre/ system has been widely used for performing cell and tissue-specific conditional analysis of gene function in zebrafish. However, simple and efficient methods for isolation of stable, Cre/ regulated zebrafish alleles are lacking. Here, we applied our GeneWeld CRISPR-Cas9 targeted integration strategy to generate floxed alleles that provide robust conditional inactivation and rescue. A universal targeting vector, UFlip, with sites for cloning short homology arms flanking a floxed 2A-mRFP gene trap, was integrated into an intron in and and integration alleles resulted in strong mRFP expression,>99% reduction of endogenous gene expression, and recapitulated known indel loss-of-function phenotypes. Introduction of Cre led to stable inversion of the floxed cassette, loss of mRFP expression, and phenotypic rescue. and integration alleles did not cause phenotypes in combination with a loss-of-function mutation. Addition of Cre led to conditional inactivation by stable inversion of the cassette, gene trapping and mRFP expression, and the expected mutant phenotype. Neural progenitor Cre drivers were used for conditional inactivation and phenotypic rescue to showcase how this approach can be used in specific cell populations. Together these results validate a simplified approach for efficient isolation of Cre/-responsive conditional alleles in zebrafish. Our strategy provides a new toolkit for generating genetic mosaics and represents a significant advance in zebrafish genetics.
Topics: Alleles; Animals; CRISPR-Cas Systems; Integrases; Zebrafish
PubMed: 35713402
DOI: 10.7554/eLife.71478 -
Wiley Interdisciplinary Reviews.... 2015The zebrafish lateral line is a sensory system used to detect changes in water flow. It is comprised of clusters of mechanosensory hair cells called neuromasts. The... (Review)
Review
The zebrafish lateral line is a sensory system used to detect changes in water flow. It is comprised of clusters of mechanosensory hair cells called neuromasts. The lateral line is initially established by a migratory group of cells, called a primordium, that deposits neuromasts at stereotyped locations along the surface of the fish. Wnt, FGF, and Notch signaling are all important regulators of various aspects of lateral line development, from primordium migration to hair cell specification. As zebrafish age, the organization of the lateral line becomes more complex in order to accommodate the fish's increased size. This expansion is regulated by many of the same factors involved in the initial development. Furthermore, unlike mammalian hair cells, lateral line hair cells have the capacity to regenerate after damage. New hair cells arise from the proliferation and differentiation of surrounding support cells, and the molecular and cellular pathways regulating this are beginning to be elucidated. All in all, the zebrafish lateral line has proven to be an excellent model in which to study a diverse array of processes, including collective cell migration, cell polarity, cell fate, and regeneration.
Topics: Animals; Cell Movement; Embryo, Nonmammalian; Hair Cells, Auditory; Lateral Line System; Models, Biological; Regeneration; Signal Transduction; Zebrafish
PubMed: 25330982
DOI: 10.1002/wdev.160