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At least 685 records · Page 38Linked to original sources
PubMed2005

Early steps in neural crest specification.

The neural crest is a multipotent cell population that arise at the border of the neural plate and non-neural ectoderm. Studies conducted in a number of model organisms including chickens, frogs, zebrafish and mice have been instrumental in elucidating this molecular mechanisms underlying neural crest formation. Signaling molecules of the Wnt, BMP, and FGF families and their downstream effectors have been shown to mediate neural crest induction. Transcription factors including members of the Snail and SoxE gene families as well as FoxD3, c-Myc and others have been implicated in specification of the neural crest. These studies represent an important step in understanding the regulatory interactions involved in generating this complex and interesting cell type.

Animals↗
PubMed2002

Forward and reverse genetic approaches to the analysis of eye development in zebrafish.

The zebrafish has been established as a mainstream research system, largely due to the immense success of genetic screens. Over 2000 mutant alleles affecting zebrafish's early development have been isolated in two large-scale morphological screens and several smaller efforts. So far, over 50 mutant strains display retinal defects and many more have been shown to affect the retinotectal projection. More recently, mutant isolation and characterization have been successfully followed by candidate and positional cloning of underlying genes. To supplement forward genetic mutational analysis, several reverse genetic techniques have also been developed. These recent advances, combined with the genome project, have established the zebrafish as one of the leading models for studies of visual system development.

Animals↗
PubMed2004

Environmental genomics: a key to understanding biology, pathophysiology and disease.

Recent advances in human and molecular genetics provide an unparalleled opportunity to understand how genes and genetic changes interact with environmental stimuli to either preserve health or cause disease. The fields of environmental genetics and environmental genomics has enormous potential to affect our ability to accurately assess the risk of developing disease, identify and understand basic pathogenic mechanisms that are critical to disease progression, and to more precisely phenotype disease subtypes. However, the application of genetics and genomics to problems in environmental health is only the beginning yet, by itself, represents a potentially effective strategy to substantially impact morbidity and mortality. Collaborative approaches that team together environmental scientists with molecular biologists, geneticists, physiologists and physician scientists are critical to the investigation of environmental aspects of human health. Moreover, exploiting eukaryotic model systems (yeast, Caenorhabditis elegans, zebrafish, Drosophila and rodents) will accelerate our understanding of environmental exposures on human health.

Biology↗
PubMed2004

Functional genomics approaches in arthritis.

The post-genomic era of functional genomics and target validation will allow us to narrow the bridge between clinically correlative data and causative data for complex diseases, such as arthritis, for which the etiological agent remains elusive. The availability of human and other annotated genome sequences, and parallel developments of new technologies that allow analysis of minute amounts of human and animal cells (peripheral blood cells and infiltrating cells) and tissues (synovium and cartilage) under different pathophysiological conditions, has facilitated high-throughput gene mining approaches that can generate vast amounts of clinically correlative data. Characterizing some of the correlative/causative genes will require reverting to the hypothesis-driven, low throughput method of complementary experimental biology using genomic approaches as a tool. This will include in silico gene expression arrays, genome-wide scans, comparative genomics using various animal models (such as rodents and zebrafish), bioinformatics and a team of well trained translational scientists and physicians. For the first time, the "genomic tools" will allow us to analyze small amounts of surgical samples (such as needle biopsies) and clinical samples in the context of the whole genome. Preliminary genomic analysis in osteoarthritis has already resurrected the debate on the semantic issues in the definition of inflammation. Further analyses will not only facilitate the development of unbiased hypotheses at the molecular level, but also assist us in the identification and characterization of novel targets and disease markers for pharmacological intervention, gene therapy, and diagnosis.

Animals↗
PubMed2004

The use of zebrafish to understand immunity.

For decades immunologists have relied heavily on the mouse model for their experimental designs. With the realization of the important role innate immunity plays in orchestrating immune responses, invertebrates such as worms and flies have been added to the repertoire. Here, we discuss the advent of the zebrafish as a powerful vertebrate model organism that promises to positively impact immunologic research.

Animals↗
PubMed2006

A keratin 18 transgenic zebrafish Tg(k18(2.9):RFP) treated with inorganic arsenite reveals visible overproliferation of epithelial cells.

Inorganic arsenic has strong human carcinogenic potential, but the availability of an animal model to study toxicity is extremely limited. Here, we used the transgenic zebrafish line Tg(k18(2.9):RFP) as an animal model to study arsenite toxicity. This line was chosen because the red fluorescent protein (RFP) is expressed in stratified epithelia (including skin), due to the RFP reporter driven by the promoter of the zebrafish keratin 18 gene. We titrated doses of inorganic arsenite for zebrafish embryos and found that arsenite exposure at 50 microM for 120 h was suitable for mimicking a long-term, chronic effect. When embryos derived from Tg(k18(2.9):RFP) adults were treated with this arsenite dose and time of exposure, abnormal phenotypes were not noticeable under the light microscope. However, arsenic keratosis was visible in the epithelial cells under the fluorescent microscope. Morphological defects became more severe with increased dose and exposure duration, suggesting that the severity of skin lesions was dose- and time-dependent. Histochemical examination of keratosis after 4',6'-diamidino-2-phenylindole hydrochloride (DAPI) staining showed that the epithelial cells overproliferated after treatment with arsenite. Therefore, this Tg(k18(2.9):RFP) zebrafish line is an excellent model for studying toxicity induced by inorganic arsenite and may have potential for studying other environmental pollutants.

Animals↗
PubMed1993

Something's fishy here--rethinking cell movements and cell fate in the zebrafish embryo.

A recent paper has challenged the prevailing view that zebrafish blastomeres undergo extensive cell mixing and are unrestricted in their cell fates during early development. Here, we offer a model that resolves apparent contradictions between studies that have examined the origins of cell fate in the zebrafish embryo. The model reconsiders cell movements during epiboly, and how cell mixing, or the lack of it, can affect the predictability of cell fate.

Animals↗
PubMed1999

Pattern formation in zebrafish--fruitful liaisons between embryology and genetics.

Vertebrate embryos, despite quite diverse early morphologies, appear to employ similar cellular strategies and conserved biochemical pathways in their development (Eyal-Giladi, 1997). In the past decade, a small tropical teleost, zebrafish (Danio rerio), became an important model system in which to study development (Streisinger et al., 1981). By combining embryology with molecular and classical genetic methods, our understanding of early inductive and morphogenetic events during vertebrate embryogenesis significantly advanced. In zebrafish, dorsal-ventral polarity is established during early cleavage and is dependent on microtubular transport of determinants from the vegetal pole to the blastomeres positioned on top of the yolk cell. The syncytium forming from these marginal blastomeres in the early blastula exhibits dorsal-ventral asymmetry with beta-catenin localized to the nuclei on the presumptive dorsal side of the syncytium. The yolk cell is a source of signals that induce and pattern overlying blastoderm. Therefore, the dorsal yolk syncytial layer is equivalent to the Nieuwkoop center of the amphibian embryo. The embryonic shield, a thickening of the dorsal blastoderm margin, exhibits properties similar to the amphibian Spemann organizer. However, certain inductive and patterning signals from the organizer might be produced before the shield forms or might originate outside of the shield. Similar to the amphibian embryo, the key patterning functions of the fish dorsal organizer (i.e., dorsalization of mesoderm, ectoderm, and coordination of gastrulation movements) are performed by secreted molecules that antagonize the ventralizing activity of the swil (zbmp-2) and zbmp-4 gene products expressed on the ventral side of the embryo. These functions of the dorsal organizer require the activity of the chordino gene (a zebrafish homologue of chordin), bozozok, mercedes and ogon loci.

Animals↗
PubMed2003

Unique and conserved aspects of gut development in zebrafish.

Although the development of the digestive system of humans and vertebrate model organisms has been well characterized, relatively little is known about how the zebrafish digestive system forms. We define developmental milestones during organogenesis of the zebrafish digestive tract, liver, and pancreas and identify important differences in the way the digestive endoderm of zebrafish and amniotes is organized. Such differences account for the finding that the zebrafish digestive system is assembled from individual organ anlagen, whereas the digestive anlagen of amniotes arise from a primitive gut tube. Despite differences of organ morphogenesis, conserved molecular programs regulate pharynx, esophagus, liver, and pancreas development in teleosts and mammals. Specifically, we show that zebrafish faust/gata-5 is a functional ortholog of gata-4, a gene that is essential for the formation of the mammalian and avian foregut. Further, extraembryonic gata activity is required for this function in zebrafish as has been shown in other vertebrates. We also show that a loss-of-function mutation that perturbs sonic hedgehog causes defects in the development of the esophagus that parallel those associated with targeted disruption of this gene in mammals. Perturbation of sonic hedgehog also affects zebrafish liver and pancreas development, and these effects occur in a reciprocal fashion, as has been described during mammalian liver and ventral pancreas development. Together, these data define aspects of digestive system development necessary for the characterization of zebrafish mutants. Given the similarities of teleost and mammalian digestive physiology and anatomy, these findings have implications for developmental and evolutionary studies as well as research of human diseases, such as diabetes, liver cirrhosis, and cancer.

Alleles↗
PubMed2003

Transplantation and in vivo imaging of multilineage engraftment in zebrafish bloodless mutants.

The zebrafish is firmly established as a genetic model for the study of vertebrate blood development. Here we have characterized the blood-forming system of adult zebrafish. Each major blood lineage can be isolated by flow cytometry, and with these lineal profiles, defects in zebrafish blood mutants can be quantified. We developed hematopoietic cell transplantation to study cell autonomy of mutant gene function and to establish a hematopoietic stem cell assay. Hematopoietic cell transplantation can rescue multilineage hematopoiesis in embryonic lethal gata1-/- mutants for over 6 months. Direct visualization of fluorescent donor cells in embryonic recipients allows engraftment and homing events to be imaged in real time. These results provide a cellular context in which to study the genetics of hematopoiesis.

Animals↗
PubMed2004

The effects of temperature reduction on gene expression and oxidative stress in skeletal muscle from adult zebrafish.

Longevity is inversely proportional to ambient temperature in ectothermic organisms such as fish. However, the mechanism by which reducing temperature over a physiological range increases life span is not known and available data are derived primarily from invertebrates. With a rodent-like longevity and abundant biological resources, the zebrafish is an ideal vertebrate ectothermic model in which to investigate this phenomenon. As an initial approach, the effects of a year-long 10 degrees C reduction in water temperature on global gene expression in tail skeletal muscle from adult zebrafish were determined using an oligonucleotide microarray representing 15,512 genes. Expression levels for approximately 600 genes were up-regulated by 1.7-fold or greater by the reduction in temperature, while a similar number of transcripts were down regulated by more than 1.7-fold. Using gene ontology (GO) classifications for molecular function, two functional groups, "oxygen and reactive oxygen species metabolism" and "response to oxidative stress," were found to be overrepresented among up-regulated genes. Transcripts levels for the genes in these two categories were increased by temperature reduction (TR). However, temperature reduction did not suppress lipid peroxidation potential, protein carbonyl content, or 8-oxoguanine level. Additional studies will be required to further delineate the role of altered gene expression and oxidative stress on the longevity-promoting effects of temperature reduction.

Aging↗
PubMed2002

Clock mechanisms in zebrafish.

Recent research on the circadian system of the zebrafish is reviewed. This teleost has become an attractive model system because of its advantages for genetic analyses. Circadian rhythms of zebrafish behavior, visual system function, and pineal melatonin synthesis have been described, and behavioral and pineal rhythms are being used to identify and characterize clock mutants. Zebrafish heart, kidney, and embryonic cell lines contain circadian oscillators and phototransduction mechanisms for entrainment, suggesting that circadian pacemaking functions may be distributed throughout the animal. Studies of circadian system development in zebrafish have found that a molecular circadian oscillation in unfertilized oocytes persists through embryonic development with its phase intact, but that the pacemakers that drive rhythms of melatonin synthesis and behavior require environmental entraining signals late in development for initial synchronization. Zebrafish homologs of several of the core clock genes identified in other animals have been cloned. Transcripts for most of these are rhythmically expressed in multiple tissues. The interactions of clock gene products are for the most part similar to their interactions in mammals, although there are some potentially interesting differences.

Animals↗
PubMed2000

Control of motor axon guidance in the zebrafish embryo.

The zebrafish neuromuscular system has been an exemplary model for studying motor axon guidance since its detailed characterization almost two decades ago. In particular, characterization and detailed analysis has focused on the development and axogenesis of early developing primary motoneurons. During the first day of development, neuromuscular connections are limited to three primary motoneurons per spinal cord hemisegment innervating three discreet myotome territories. Observations of dye labeled primary motor axons in living embryos revealed that axogenesis is highly stereotyped with each primary motor axon extending along specific pathways and displaying particular characteristics. Exploiting the unique attributes of zebrafish, notably the ability to analyze motoneurons in living embryos and the capability to induce mutations, has allowed a comprehensive cellular, molecular and genetic approach to discerning the mechanisms that control the formation of neuromuscular connectivity. Knowledge gained from this body of work not only relates to zebrafish, but to vertebrate axon guidance in general.

Animals↗
PubMed1994

Integration and germ-line transmission of a pseudotyped retroviral vector in zebrafish.

The zebrafish is rapidly becoming a popular model system for the study of vertebrate development because it is ideal for both embryological studies and genetic analysis. To determine if a retroviral vector pseudotyped with the envelope glycoprotein of the vesicular stomatitis virus could infect zebrafish embryos, and in particular, the cells destined to become the germ line, a pseudotyped virus was injected into blastula-stage zebrafish embryos. Fifty-one embryos were allowed to develop and eight transmitted proviral DNA to their progeny. Founders were mosaic, but as expected, transgenic F1's transmitted proviral DNA in a Mendelian fashion to the F2 progeny. Transgenic F1 fish inherited a single integrated provirus, and a single founder could transmit more than one viral integration to its progeny. These results demonstrate that this pantropic pseudotyped vector, originally developed for human gene therapy, will make the use of retroviral vectors in zebrafish possible.

Animals↗
PubMedDate not supplied

Mapping absorbance spectra, cone fractions, and neuronal mechanisms to photopic spectral sensitivity in the zebrafish.

The four spectral cone types in the zebrafish retina each contribute to photopic visual sensitivity as measured by the b-wave of the electroretinogram (ERG). The goal of the current study was to evaluate a model of photopic b-wave spectral sensitivity in the zebrafish that mapped first-order cellular and biophysical aspects of cone photoreceptors (visual pigment absorbance spectra and cone fractions) onto a second-order physiological aspect of cone-derived neural activity in the retina. Good correspondence between the model and photopic ERG data was attained using new visual pigment absorbance data for zebrafish cones (lambda(max) of the L, M, and S cones were 564, 473, and 407 nm, respectively), visual pigment templates, and linearly gained cone fractions. The model inferred four distinct cone processing channels that contribute to the photopic b-wave, two of which are antagonistic combinations of cone-derived signals (L-M and M-S), and two of which are noncombinatorial signals from S and U cones. The nature of the gains and the processing channels suggested general rules of cone-specific inputs to second-order neurons. The model further suggested that the zebrafish retina utilizes neuronal mechanisms for enhancing sensitivity to luminance contrast at short wavelengths and chromatic contrast at middle and long wavelengths. The results indicated that first-order cellular and biophysical aspects of cone photoreceptors can successfully explain physiological aspects of cone-derived neuronal activity in the zebrafish retina.

Animals↗
PubMed2003

Making a zebrafish kidney: a tale of two tubes.

The kidney can be thought of as the pairing of two tubes: an epithelial tube (the nephron), carrying filtered blood and engaged in ion and water transport; and endothelial tubes (the blood vessels), delivering blood and carrying away recovered solute. The development of the nephron presents several interesting questions. How does an epithelial tube form and how is it patterned into functionally distinct components and segments? What guides the interaction between the vasculature and kidney epithelia? How are epithelial cell shape and lumen diameter maintained, and what goes wrong when kidney tubules balloon into cysts? Here, I outline the progress that has been made in answering these questions using the zebrafish pronephros as a simple, accessible model of nephron development.

Animals↗
PubMed2003

The rice field eel as a model system for vertebrate sexual development.

Complex developmental mechanisms of vertebrates are unraveled using comparative genomic approaches. Several teleosts, such as zebrafish, medaka and pufferfish, are used as genetic model systems because they are amenable to studies of gene function. The rice field eel, a freshwater fish, is emerging as a specific model system for studies of vertebrate sexual development because of its small genome size and naturally occurring sex reversal. Data presented here support the use of the rice field eel as another important fish model for comparative genome studies, especially in vertebrate sexual development. This model system is complementary rather than redundant.

Animals↗
PubMed2001

Pattern formation in the zebrafish retina.

During the past 15 years, the zebrafish has become established as a genetic model organism to study vertebrate development. It is particularly well suited for the analysis of the retina, and several genetic screens have yielded a large number of mutants affecting retinal development. Most of these mutants still await thorough analysis and molecular characterization, but work on a handful of genes has already generated interesting results that shed some light on patterning mechanisms employed in the vertebrate retina.

Animals↗