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At least 451 records · Page 25Linked to original sources
PubMed2003

Interactions between 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and hypoxia signaling pathways in zebrafish: hypoxia decreases responses to TCDD in zebrafish embryos.

The aryl hydrocarbon receptor (AHR) interacts with the aryl hydrocarbon receptor nuclear translocator (ARNT) to form a heterodimer that binds to promoters in target genes to alter transcription in response to xenobiotics such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The ARNT protein also forms heterodimers with other proteins such as HIF-1alpha and HIF-2alpha to alter gene expression in response to low oxygen conditions. Because ARNT is shared between multiple signaling pathways it is possible that activation of one ARNT-requiring pathway could inhibit the activation of other pathways that depend on ARNT. One hypothesis to explain TCDD toxicity in early life stage fish is that TCDD activation of zfAHR2 sequesters zfARNT2 away from the hypoxia signaling pathway. To test this hypothesis we measured the ability of TCDD to prevent induction of heme oxygenase by hypoxia (40% saturation), as well as the ability of hypoxia to increase the sensitivity of zebrafish to the effects of TCDD during the first week of life. As a further test of the model we examined mutant zebrafish that lack zfARNT2 for phenotypes that resemble the effects of TCDD exposure. Our results demonstrate that sequestration of zfARNT2 is not causing TCDD toxicity. TCDD did not inhibit hypoxia induction of heme oxygenase, hypoxia and TCDD exposures were not additive in causing developmental toxicity, and mutant embryos that lack zfARNT2 do not develop defects mimicking TCDD toxicity. However, our results demonstrate some level of cross talk between the two pathways in the zebrafish embryo. Hypoxia decreased TCDD induction of zfCYP1A mRNA, and decreased the potency of TCDD in causing edema. It is not clear whether this is mediated through competition for zfARNT2, or through other mechanisms.

Animals↗
PubMed2006

Caspase-3 induced apoptosis in transgenic zebrafish.

Zebrafish is an attractive model organism for studying apoptosis development because of its genetic accessibility. Here we describe the induction of clonally derived apoptosis in transgenic zebrafish expressing mouse caspase-3 (CASP3) under control of the zebrafish beta-actin promoter (betap). Visualization of apoptotic cells, expressing a chimeric transgene encoding CASP3 fused to green fluorescent protein (GFP) gene, revealed that apoptosis arose in the thymus, spread locally into gill arches and retro-orbital soft tissue, and then disseminated into abdominal organs like testis, kidney. This transgenic model provides a platform for over-expression of caspase-3 induced extensive apoptosis in embryos and adult.

Actins↗
PubMed2006

Fgf21 is essential for haematopoiesis in zebrafish.

Fibroblast growth factors (Fgfs) function as key secreted signalling molecules in many developmental events. The zebrafish is a powerful model system for the investigation of embryonic vertebrate haematopoiesis. Although the effects of Fgf signalling on haematopoiesis in vitro have been reported, the functions of Fgf signalling in haematopoiesis in vivo remain to be explained. We identified Fgf21 in zebrafish embryos. Fgf21-knockdown zebrafish embryos lacked erythroid and myeloid cells but not blood vessels and lymphoid cells. The knockdown embryos had haemangioblasts and haematopoietic stem cells. However, the knockdown embryos had significantly fewer myeloid and erythroid progenitor cells. In contrast, Fgf21 had no significant effect on cell proliferation and apoptosis in the intermediate cell mass. These results indicate that Fgf21 is a newly identified factor essential for the determination of myelo-erythroid progenitor cell fate in vivo.

Animals↗
PubMed2005

Interplay of pu.1 and gata1 determines myelo-erythroid progenitor cell fate in zebrafish.

The zebrafish is a powerful model system for investigating embryonic vertebrate hematopoiesis, allowing for the critical in vivo analysis of cell lineage determination. In this study, we identify zebrafish myeloerythroid progenitor cells (MPCs) that are likely to represent the functional equivalent of mammalian common myeloid progenitors. Utilizing transgenic pu.1-GFP fish, real-time MPC differentiation was correlated with dynamic changes in cell motility, morphology, and gene expression. Unlike mammalian hematopoiesis, embryonic zebrafish myelopoiesis and erythropoiesis occur in anatomically separate locations. Gene knockdown experiments and transplantation assays demonstrated the reciprocal negative regulation of pu.1 and gata1 and their non-cell-autonomous regulation that determines myeloid versus erythroid MPC fate in the distinct blood-forming regions. Furthermore, forced expression of pu.1 in the bloodless mutant cloche resulted in myelopoietic rescue, providing intriguing evidence that this gene can function in the absence of some stem cell genes, such as scl, in governing myelopoiesis.

Animals↗
PubMed2005

Pentylenetetrazole induced changes in zebrafish behavior, neural activity and c-fos expression.

Rodent seizure models have significantly contributed to our basic understanding of epilepsy. However, medically intractable forms of epilepsy persist and the fundamental mechanisms underlying this disease remain unclear. Here we show that seizures can be elicited in a simple vertebrate system e.g. zebrafish larvae (Danio rerio). Exposure to a common convulsant agent (pentylenetetrazole, PTZ) induced a stereotyped and concentration-dependent sequence of behavioral changes culminating in clonus-like convulsions. Extracellular recordings from fish optic tectum revealed ictal and interictal-like electrographic discharges after application of PTZ, which could be blocked by tetrodotoxin or glutamate receptor antagonists. Epileptiform discharges were suppressed by commonly used antiepileptic drugs, valproate and diazepam, in a concentration-dependent manner. Up-regulation of c-fos expression was also observed in CNS structures of zebrafish exposed to PTZ. Taken together, these results demonstrate that chemically-induced seizures in zebrafish exhibit behavioral, electrographic, and molecular changes that would be expected from a rodent seizure model. Therefore, zebrafish larvae represent a powerful new system to study the underlying basis of seizure generation, epilepsy and epileptogenesis.

Animals↗
PubMed2000

Characterization of zebrafish full-length prothrombin cDNA and linkage group mapping.

In this paper, we report the complete cDNA sequence of zebrafish prothrombin. The cDNA sequence predicts that zebrafish prothrombin is synthesized as a pre-proprotein consisting of a Gla domain, two kringle domains, and a two-chain protease domain. Zebrafish prothrombin is structurally very similar to human and other vertebrate prothrombins. Zebrafish and human prothrombin share 53% amino acid identity whereas zebrafish and hagfish prothrombin share 51% identity. Amino acid alignments of various prothrombins identified conservation of many of the functional/structural motifs suggesting that the vertebrate prothrombins may have similar functions. The three-dimensional structure of prothrombin predicted by homology modeling also revealed that the prothrombin fragment 1 and the catalytic domain structures are well conserved except for the insertion of an extra 7-amino-acid loop in the connecting region (CR) between the Gla and kringle I domain of fragment 1. Linkage analysis revealed that the prothrombin gene locus on linkage group 7 in zebrafish is syntenic to the human chromosome 11-prothrombin region suggesting its preservation through evolution. The availability of this cDNA sequence in zebrafish adds to our knowledge of the zebrafish hemostatic system and provides support for the view that similarities between zebrafish and mammalian coagulation exist, thus underscoring the relevance of the zebrafish model for studying human hemostasis.

Amino Acid Sequence↗
PubMedDate not supplied

Analysis of blood coagulation in the zebrafish.

The zebrafish (Danio rerio) is a unique animal model in which saturation mutagenesis has been used to identify genes involved in vertebrate development. The relevance of the zebrafish as a genetic model for hemostasis depends, in large part, on the degree of similarity between the zebrafish and mammalian systems. The diminutive size of the zebrafish poses technical problems for analysis of coagulation. This study describes methods to obtain citrated whole blood and plasma from the zebrafish, analyze in vitro coagulation in small plasma volumes, obtain uniform dosing of zebrafish with oral anticoagulants, and demonstrate specific factor activities via chromogenic assays. Analysis of the zebrafish system demonstrates the presence of both the intrinsic and extrinsic pathways of coagulation, evidence for prothrombin, factor X, protein C, antithrombin, and heparin cofactor II activity, and a requirement for vitamin K dependent gamma-carboxylation of zebrafish hemostatic proteins. Induction of a morphologically recognizable bleeding phenotype by warfarin treatment is also demonstrated. Characterization of zebrafish coagulation provides evidence that major hemostatic pathways are conserved between zebrafish and man. These similarities indicate that the zebrafish is a relevant genetic model for identification of novel genes involved in hemostasis and thrombosis.

Animals↗
PubMed2002

Light induction of a vertebrate clock gene involves signaling through blue-light receptors and MAP kinases.

The signaling pathways that couple light photoreception to entrainment of the circadian clock have yet to be deciphered. Two prominent groups of candidates for the circadian photoreceptors are opsins (e.g., melanopsin) and blue-light photoreceptors (e.g., cryptochromes). We have previously showed that the zebrafish is an ideal model organism in which to study circadian regulation and light response in peripheral tissues. Here, we used the light-responsive zebrafish cell line Z3 to dissect the response of the clock gene zPer2 to light. We show that the MAPK (mitogen-activated protein kinase) pathway is essential for this response, although other signaling pathways may also play a role. Moreover, action spectrum analyses of zPer2 transcriptional response to monochromatic light demonstrate the involvement of a blue-light photoreceptor. The Cry1b and Cry3 cryptochromes constitute attractive candidates as photoreceptors in this setting. Our results establish a link between blue-light photoreceptors, probably cryptochromes, and the MAPK pathway to elicit light-induced transcriptional activation of clock genes.

Adaptation, Ocular↗
PubMedDate not supplied

Issues related to the use of fish models in toxicologic pathology: session introduction.

Ready or not, fish models are "here to stay." No longer are fish confined to a few specialized laboratories, nor are they exclusively the purview of zoologists or environmental toxicologists. In fact, the institution that does not house at least 1 fish facility is probably not at the forefront of cutting edge research. In toxicologic pathology, fish models are increasingly being used to provide high animal numbers at relatively low cost in carcinogenicity testing and developmental research, and to provide mechanistic information on fundamental cellular processes. In this session, we attempt to provide some perspective for the pathologist that is faced with planning or performing experiments or testing protocols using fish models, or with reading or interpreting fish studies. First, we cover how to approach fish studies from the contract laboratory standpoint, including sectioning, quality control, and GLP considerations. Then, we discuss specifics on the use of the rainbow trout, zebrafish, and Japanese medaka models. The rainbow trout has a rich history in carcinogenicity and mechanistic cancer research. Similarly, the 2 workhorses in the small fish category, zebrafish and medaka, have found their way into many laboratories doing developmental biology and genomics research as well as carcinogenicity testing. Some fascinating genetically altered fish models have been developed with both of these species. This manuscript provides a session overview of the use of small fish models in toxicologic pathology, along with some historical perspective on how these models have played a role in the current state of the science.

Animals↗
PubMed2003

[Neurosurgical embryology. Part 6: The principal models that can be used in developmental biology].

To study the mechanisms controlling embryonic development, experimental analyses must be performed on animal models. There are different species that are currently used as models in developmental biology. In invertebrates, drosophila remains a very useful model thanks to its rapid development and to the extensive study of genes involved in the control of its development. C. elegans has been extensively used because of its simplicity due to the total restricted number of adult cells in this species. In vertebrates, amphibians remain a very useful model with the extensive analysis of Xenopus laevis. The zebrafish is now a widely used model because of its genetic analysis. Birds are still used for the accessibility of their embryo allowing experimental procedures to be performed in ovo. The mouse is now very widely used because it is possible to obtain transgenic mice to study both loss or gain of gene function.

Animals↗
PubMed2003

Myc-induced T cell leukemia in transgenic zebrafish.

The zebrafish is an attractive model organism for studying cancer development because of its genetic accessibility. Here we describe the induction of clonally derived T cell acute lymphoblastic leukemia in transgenic zebrafish expressing mouse c-myc under control of the zebrafish Rag2 promoter. Visualization of leukemic cells expressing a chimeric transgene encoding Myc fused to green fluorescent protein (GFP) revealed that leukemias arose in the thymus, spread locally into gill arches and retro-orbital soft tissue, and then disseminated into skeletal muscle and abdominal organs. Leukemic cells homed back to the thymus in irradiated fish transplanted with GFP-labeled leukemic lymphoblasts. This transgenic model provides a platform for drug screens and for genetic screens aimed at identifying mutations that suppress or enhance c-myc- induced carcinogenesis.

Animals↗
PubMed1996

Large scale genetics in a small vertebrate, the zebrafish.

The systematic isolation and characterization of mutants in Drosophila has enormously facilitated the analysis of molecular mechanisms underlying developmental pathways in the embryo. A similar approach is presently being used to study embryonic development of the zebrafish, which is becoming a mainstream model organism for vertebrate development. With its genetic versatility and sophisticated embryology, zebrafish offers the possibility to rapidly increase our knowledge of vertebrate development and add to what we have learned from other vertebrate model organisms.

Animals↗
PubMed2006

Contribution of mGluR and Fmr1 functional pathways to neurite morphogenesis, craniofacial development and fragile X syndrome.

Fragile X Syndrome is a leading heritable cause of mental retardation that results from the loss of FMR1 gene function. Studies in mouse and Drosophila model organisms have been critical in understanding many aspects of the loss of function of the FMR1 gene in the human syndrome. Here, we establish that the zebrafish is a useful model organism for the study of the human fragile X syndrome and can be used to examine phenotypes that are difficult or inaccessible to observation in other model organisms. Using morpholino knockdown of the fmr1 gene, we observed abnormal axonal branching of Rohon-Beard and trigeminal ganglion neurons and guidance and defasciculation defects in the lateral longitudinal fasciculus. We demonstrate that this axonal branching defect can be rescued by treatment with MPEP [2-methyl-6-(phenylethynyl) pyridine]. This is consistent with an interaction between mGluR signalling and fmr1 function in neurite morphogenesis. We also describe novel findings of abnormalities in the abundance of trigeminal ganglion neurons and of craniofacial abnormalities apparently due to dysmorphic cartilage formation. These abnormalities may be related to a role for fmr1 in neural crest cell specification and possibly in migration.

Animals↗
PubMed2002

Organogenesis--heart and blood formation from the zebrafish point of view.

Organs are specialized tissues used for enhanced physiology and environmental adaptation. The cells of the embryo are genetically programmed to establish organ form and function through conserved developmental modules. The zebrafish is a powerful model system that is poised to contribute to our basic understanding of vertebrate organogenesis. This review develops the theme of modules and illustrates how zebrafish have been particularly useful for understanding heart and blood formation.

Animals↗
PubMed2004

Pathogenesis and inflammatory response to Edwardsiella tarda infection in the zebrafish.

The zebrafish (Danio rerio) is a widely used model for developmental biology, neurobiology, toxicology, and genetic disease. Recently, the zebrafish has been recognized as a valuable model for infectious disease and immunity. In this study the pathogenesis and inflammatory cytokine response of zebrafish to experimental Edwardsiella tarda infection was characterized. In challenge experiments, zebrafish embryos were susceptible to infection by immersion. Adult fish were susceptible to challenge by intraperitoneal (ip) injection but not static immersion unless the epithelial layer was perturbed by scraping prior to exposure. To determine if E. tarda infection induces a typical acute inflammatory response, mRNA expression levels of interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNFalpha) were assessed by quantitative real-time PCR. The expression levels of IL-1beta and TNFalpha were significantly upregulated in infected zebrafish embryos and adults. The methods developed in this study will be particularly valuable for targeted gene disruption studies of host immune components and in zebrafish genetic screens.

Animals↗
PubMed1995

Tubulin dynamics in neuronal axons of living zebrafish embryos.

The mechanism of cytoskeletal protein transport, especially the question of what kind of form the cytoskeletal proteins assume during transport in neurons in situ, has been an important, as yet unsettled issue. To clear up this matter, we adopted the embryonic zebrafish as a living animal model and applied the fluorescence recovery after photobleaching (FRAP) method. The zebrafish embryo is appropriate for this kind of study because of its transparency during the early developmental stage, allowing the observation of neurons that incorporate the microinjected fluorescent tubulin directly under fluorescence microscopy. FRAP revealed no movement of the bleached zone proximodistally, where fluorescence recovered gradually (recovery half-time, 44.2 +/- 11.2 min; n = 36), suggesting that the polymers are stationary but dynamic and that the true moving form could be small oligomers or heterodimers.

Animals↗
PubMed2004

Technology for high-throughput screens: the present and future using zebrafish.

The zebrafish is a popular vertebrate model organism with similar organ systems and gene sequences to humans. Zebrafish embryos are optically transparent enabling organ visualisation, which can be complemented with gene expression analysis at the transcript and protein levels. Furthermore, zebrafish can be treated with small molecules and drugs in a microtitre plate format for high-throughput analysis and for the identification and validation of drugs. High-throughput methodologies for use in zebrafish include phenotype-based visualisation, transcript studies using low-density DNA microarrays and proteomic analysis. These technologies offer significant whole-organism biological value in the drug discovery and drug development pipeline.

Animals↗