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At least 271 records · Page 15Linked to original sources

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↗

PubMed2006

Cloning and characterization of zebrafish CTCF: Developmental expression patterns, regulation of the promoter region, and evolutionary aspects of gene organization.

CTCF is a nuclear phosphoprotein capable of using different subsets of its 11 Zn fingers (ZF) for sequence-specific binding to many dissimilar DNA CTCF-target sites. Such sites were identified in the genomic DNA of various multicellular organisms, in which the CTCF gene was cloned, including insects, birds, rodents, and primates. CTCF/DNA-complexes formed in vivo with different 50-bp-long sequences mediate diverse functions such as positive and negative regulation of promoters, and organization of all known enhancer-blocking elements ("chromatin insulators") including constitutive and epigenetically regulated elements. Abnormal functions of certain CTCF sites are implicated in cancer and in epigenetic syndromes such as BWS and skewed X-inactivation. We describe here the cloning and characterization of the CTCF cDNA and promoter region from zebrafish, a valuable vertebrate model organism. The full-length zebrafish CTCF cDNA clone is 4244 bp in length with an open reading frame (ORF) of 2391 bp that encodes 797 amino acids. The zebrafish CTCF amino acid sequence shows high identity (up to 98% in the zinc finger region) with human CTCF, and perfect conservation of exon-intron organization. Southern blot analyses indicated that the zebrafish genome contains a single copy of the CTCF gene. In situ hybridization revealed the presence of zebrafish CTCF transcripts in all early stages of embryogenesis. Transfection assays with luciferase reporter-constructs identified a core promoter region within 146 bp immediately upstream of the transcriptional start site of zebrafish CTCF that is located at a highly conserved YY1/Initiator element.

Amino Acid Sequence↗

PubMed2006

Zebrafish and chicken lipocalin-type prostaglandin D synthase homologues: Conservation of mammalian gene structure and binding ability for lipophilic molecules, and difference in expression profile and enzyme activity.

Lipocalin-type prostaglandin (PG) D synthase (L-PGDS) is a bifunctional protein possessing both the ability to synthesize PGD(2) and to serve as a carrier protein for lipophilic molecules. L-PGDS has been extensively studied in mammalian species, whereas little is known about non-mammalian forms. Here, we identified and characterized the L-PGDS homologues from non-mammals such as zebrafish and chicken. Phylogenetic analysis revealed that L-PGDSs of mammalian and non-mammalian organisms form a "L-PGDS sub-family" that has been evolutionally separated from other lipocalin gene family proteins. The genes for zebrafish and chicken L-PGDS homologues consisted of 6 exons, and all of the exon/intron boundaries were completely identical to those of mammalian L-PGDS genes. Zebrafish and chicken L-PGDS genes were clustered with several lipocalin genes in the chromosome, as in the case of mouse and human genes. Gene expression profiles were different among chicken, mouse, human, except for conservation of abundant expression in the brain and heart. The chicken L-PGDS homologue carried weak PGDS activity, whereas the zebrafish protein did not show any of the activity. However, when the amino-terminal region of the zebrafish L-PGDS homologue was exchanged for that of mouse L-PGDS carrying the Cys residue essential for PGDS activity, this chimeric protein showed weak PGDS activity. Both zebrafish and chicken L-PGDS homologues bound thyroxine and all-trans retinoic acid, like mammalian L-PGDSs and other lipocalin gene family proteins. These results indicate that non-mammalian and mammalian L-PGDS genes evolved from the same ancestral gene and that the non-mammalian L-PGDS homologue was the primordial form of L-PGDS but whose major function was and is to serve as a carrier protein for lipophilic molecules. During molecular evolution, the mammalian L-PGDS protein might have acquired effective PGDS activity through substitution of several amino acid residues, especially in the amino-terminal region including the Cys residue, which is essential for PGDS activity.

Amino Acid Sequence↗

PubMed2006

Specific activation of the human HSP70 promoter by copper sulfate in mosaic transgenic zebrafish.

Heat shock proteins (HSPs) play a central role in cell protection and repair upon stresses, such as that caused by heat and heavy metals. Copper sulfate inducibility of a pHhsp70 construct expressing the enhanced green fluorescent protein (EGFP) gene under the control of the exogenous human hsp70 promoter was tested in transfected CHSE 214 cells and transgenic zebrafish (Danio rerio). We developed a transient expression system, using mosaically transgenic zebrafish, which allows rapid analysis of transgenic expression. Transfected CHSE 214 cells which had been exposed to 250 nM and 2.5 microM copper sulfate for up to 24h showed increased EGFP expression in a dose-dependent manner. The 1.5 microM copper sulfate caused stronger EGFP fluorescence than the 1.0 microM copper sulfate in transgenic zebrafish. Most of the expression was spotty and was detected in the gills, dorsal and ventral retina, myotubes of the trunk, and skin epithelium. Transgenic zebrafish exposed to copper sulfate exhibited gross dysmorphogenesis, edema and trunk abnormalities, such as spinal lordosis, in vertebral development 5 days after fertilization. This transgenic zebrafish system was sensitive enough to detect copper sulfate at doses below the median lethal concentration (the LC50 was calculated to be 1.2 microM (95% confidence interval of 0.6-1.9 microM)). These results indicate that zebrafish could be useful transgenic biosensor systems for the detection of xenobiotic toxicants in the environment.

Animals↗

PubMed2006

Gene expression patterns of the ALP family during zebrafish development.

The actinin-associated LIM protein (ALP) genes belong to the PDZ/LIM protein family which is characterized by the presence of both a PDZ and a LIM domain. The ALP subfamily in mammals has four members: ALP, Elfin, Mystique and RIL. In this study, we have annotated and cloned the zebrafish ALP gene family and identified a zebrafish-specific fifth member of the family, the alp-like gene. We compared the zebrafish sequences to their human and mouse orthologues. A phylogenetic analysis based on the amino acid sequences showed the overall high degree of conservation within the family. We describe here the expression patterns for all five ALP family genes during zebrafish development. Whole mount in situ hybridization results revealed common and distinct expression patterns for the five genes. With the exception of elfin, all genes were expressed as maternal RNAs at early developmental stages. Gene expression for all of them appeared regulated and localized in specific regions at the eight different developmental stages studied. Expression for all five genes was observed in the central nervous system (CNS), which led us to further investigate brain-specific expression in sections of embryos at 2 days of development. In summary, we identified the zebrafish orthologues of the ALP family and determined their gene expression patterns during zebrafish embryogenesis. Finally, we compare our results to the limited expression data available for this gene family during mammalian development.

Amino Acid Sequence↗

PubMed2006

V(D)J recombination in zebrafish: Normal joining products with accumulation of unresolved coding ends and deleted signal ends.

V(D)J recombination proceeds from a site-specific cleavage to an imprecise end joining, via generation and resolution of recombination ends. Although rearranged antigen receptor genes isolated from zebrafish (Danio rerio) resemble those made in mammals, differences may arise during evolution from lower to higher vertebrates, in regard to efficiency, fidelity and regulation of this recombination. To elucidate the V(D)J recombination reaction in zebrafish, we characterized recombination ends transiently produced by zebrafish lymphocytes, as well as joining products. Similar to their mammalian counterpart, zebrafish lymphocytes make perfect signal joints and normal coding joints, indicating their competent end resolution machinery. However, recombination ends recovered from the same zebrafish lymphoid tissues exhibit some features that are not readily seen in normal mammalian counterpart: deleted signal ends and accumulation of opened coding ends. These results indicate that the recombination reaction in zebrafish lymphocytes is inefficient and less stringently regulated, which may result from unstable post-cleavage complexes, and/or slow transition from cleavage to resolution. Our data suggests that the V(D)J recombination machinery may have undergone evolution selection to become more efficient in higher jawed vertebrates.

Animals↗

PubMed2006

Effects of acute and chronic ethanol exposure on the behavior of adult zebrafish (Danio rerio).

The zebrafish has been a popular subject of embryology and genetic research for the past three decades. Recently, however, the interest in its neurobiology and behavior has also increased. Nevertheless, compared to other model organisms, e.g., rodents, zebrafish behavior is understudied and very few behavioral paradigms exist for mutation or drug screening purposes. Alcoholism is one of the biggest and costliest diseases whose mechanisms are not well understood. Model organisms such as the zebrafish may be utilized in this line of research. Previously, we investigated the effects of acute ethanol exposure on adult zebrafish using four behavioral paradigms and employing manual quantification methods. Here, we study the effects of chronic ethanol exposure and analyze how it modifies the effects of acute ethanol treatment. We employ a videotracking-based automated quantification method in a predator model paradigm and show that this method is capable of detecting an avoidance reaction that is ameliorated by higher doses of ethanol, a potential anxiolytic effect. Importantly, we also demonstrate that chronic, two week long, exposure to ethanol results in significant adaptation to this substance in adult zebrafish. Overall, our results suggest that zebrafish will be an appropriate subject for high throughput screening applications aimed at the analysis of the mechanisms and pharmacology of acute and chronic ethanol induced changes in the vertebrate brain.

Alcoholism↗

PubMed2005

Studying rod photoreceptor development in zebrafish.

The zebrafish has rapidly become a favored model vertebrate organism, well suited for studies of developmental processes using large-scale genetic screens. In particular, zebrafish morphological and behavioral genetic screens have led to the identification of genes important for development of the retinal photoreceptors. This may help clarify the genetic mechanisms underlying human photoreceptor development and dysfunction in retinal diseases. In this review, we present the advantages of zebrafish as a vertebrate model organism, summarize retinal and photoreceptor cell development in zebrafish, with emphasis on the rod photoreceptors, and describe zebrafish visual behaviors that can be used for genetic screens. We then describe some of the photoreceptor cell mutants that have been isolated in morphological and behavioral screens and discuss the limitations of current screening methods for uncovering mutations that specifically affect rod function. Finally, we present some alternative strategies to target the rod developmental pathway in zebrafish.

Animals↗

PubMed2003

Zebrafish embryos express an orthologue of HERG and are sensitive toward a range of QT-prolonging drugs inducing severe arrhythmia.

A wide range of drugs has been shown to prolong the QT interval of the electrocardiogram by blocking the pore-forming subunit of the rapidly activating delayed rectifier K+ channel, HERG (ether-à-go-go-related gene), sometimes leading to life-threatening arrhythmia. In this paper we describe cloning, sequence, and expression of the zebrafish orthologue of HERG, Zerg. Further, we studied effects of Zerg inhibition in zebrafish embryos caused by drugs or by an antisense approach. Zerg is expressed specifically in both heart chambers of zebrafish embryos, is composed of six transmembrane domains, and shows an especially high degree of amino acid conservation in the S6 and pore domain (99% identity). Several QT-prolonging drugs added to the bathing medium elicited bradycardia and arrhythmia in zebrafish embryos. The arrhythmia induced ranged from an atrioventricular 2:1 block, the ventricle beating half as often as the atrium, to more severe irregular arrhythmia with higher concentrations of the drugs. These effects were highly specific, reproducible, and rapid, e.g., 10 microM astemizole caused a 2:1 heartbeat within a minute after addition of the compound in all the embryos studied. Morpholino antisense oligonucleotides targeting Zerg were injected into zebrafish embryos and elicited similar dose-sensitive and specific arrhythmia as the QT-prolonging drugs, suggesting an evolutionarily conserved role for Erg in regulating heartbeat rate and rhythm. Further, we identified a mutation in the Per-Arnt-Sim domain of the Zerg channel in the breakdance mutant, also characterized by a 2:1 atrioventricular block. In conclusion, the zebrafish could be a tractable model organism for the study of Erg function and modulation but might also have a value in the field of cardiovascular pharmacology, e.g., as an early preclinical model for testing drugs under development for potential QT prolongation.

Animals↗

PubMed2006

Small molecule screening in the zebrafish.

The zebrafish is an ideal organism for small molecule studies. The ability to use the whole organism allows complex in vivo phenotypes to be assayed and combines animal testing with screening. Embryos are easily treatable by waterborne exposure. The small size and abundance of embryos make zebrafish suitable for screening in a high-throughput manner in 96- or 48-well plates. Zebrafish embryos have successfully been used in chemical genetic screens to elucidate biological pathways and find chemical suppressors. Small molecules discovered by screening zebrafish disease models may also be useful as lead compounds for drug development as there appears to be a high level of conservation of drug activity between mammals and zebrafish. Here we provide the technical aspects of treating embryos with small molecules and performing chemical screens with zebrafish.

Animals↗

PubMed2003

cDNA cloning, expression, and functional characterization of a zebrafish SULT1 cytosolic sulfotransferase.

Using the reverse transcriptase-polymerase chain reaction technique, a full-length cDNA encoding a novel zebrafish sulfotransferase was cloned and sequenced. Sequence analysis indicated that this zebrafish sulfotransferase belongs to the SULT1 cytosolic sulfotransferase gene family. The recombinant form of the zebrafish sulfotransferase, purified from Escherichia coli cells, displayed sulfating activities toward a number of endogenous compounds, in particular dopamine and thyroid hormones, in addition to xenobiotics including some flavonoids, isoflavonoids, and other phenolic compounds. The zebrafish sulfotransferase exhibited substrate dependence in pH optimum. In comparison with those determined with dopamine as substrate, the zebrafish sulfotransferase displayed much lower K(m) and higher V(max) with n-propyl gallate as substrate. A thermostability experiment revealed the enzyme to be relatively stable over a temperature range between 20 and 43 degrees C. Among 10 divalent metal cations tested, Hg(2+), Co(2+), Zn(2+), Cd(2+), Cu(2+), and Pb(2+) exhibited dramatic inhibitory effects on the activity of the zebrafish sulfotransferase.

Animals↗

PubMed2003

Gonadotropin regulation of follistatin expression in the cultured ovarian follicle cells of zebrafish, Danio rerio.

Follistatin is a single-chain glycoprotein initially identified in the mammalian ovary. As a specific binding protein of activin, it effectively modifies the paracrine/autocrine roles of activin in a variety of tissues including the ovary. In the zebrafish, we have demonstrated that the human chorionic gonadotropin (hCG)-induced oocyte maturation and oocyte maturational competence can be blocked by follistatin, suggesting a role for ovarian activin in the signaling pathway of gonadotropin in the zebrafish ovary. The up-regulation of zebrafish ovarian activin betaA subunit by gonadotropin further supports this hypothesis. Since follistatin has extremely high affinity for activin, its expression level in various tissues is critical in fine-tuning local activin activities. In the present study, we investigated the regulation of follistatin expression by gonadotropin in a primary culture of zebrafish ovarian follicle cells using semi-quantitative RT-PCR. Both hCG and goldfish pituitary extract strongly increased the expression of follistatin in the cultured follicle cells in clear time- and dose-dependant manners. The effect of hCG (15IU/ml) reached the maximal level at 2h of treatment and longer treatment (4-8h) led to decreased response. The up-regulation of follistatin expression by hCG could be mimicked by all the drugs that increase the intracellular cAMP level including 8-Br-cAMP, db-cAMP, forskolin, and 3-isobutyl-1-methylxanthine (IBMX). The hCG (15IU/ml)- and forskolin (10microM)-induced follistatin expression could be blocked by H89 (10microM), a specific protein kinase A (PKA) inhibitor. These results strongly suggest that the regulation of follistatin expression in the zebrafish ovary by gonadotropin is primarily mediated by cAMP-PKA signaling pathway. The up-regulation of follistatin mRNA by gonadotropin in cultured zebrafish ovarian follicle cells, together with our previous studies on gonadotropin regulation of activin beta subunits, suggests that the ovarian activin-follistatin system is tightly controlled by gonadotropin in fish ovary.

Activins↗

PubMed2004

Vascular endothelial growth factor and its receptors in embryonic zebrafish blood vessel development.

There is intense interest in how blood vessel development is regulated. A number of vascular growth factors and their receptors have been described. The vascular endothelial growth factor (VEGF) and its receptors are major contributors to normal mammalian vascular development. These receptors include VEGFR-1, VEGFR-2, VEGFR-3, neuropilin-1 (NRP1), and NRP2. The function of these genes have been determined to some degree in mouse gene targeting studies. These knockouts are embryonically lethal, and early death can be attributed in part to lack of normal blood and lymphatic vessel development. More recently, it has been demonstrated that zebrafish are an excellent model for studying the genes and proteins that regulate embryonic vascular development. Zebrafish have a number of advantages compared to mice, including rapid embryonic development and the ability to examine and manipulate embryos outside of the animal. In this review, we describe some of the earlier mouse VEGF/receptor functional studies and emphasize the development of the zebrafish vasculature. We describe the zebrafish vasculature, zebrafish VEGF and VEGF receptors, advantages of the zebrafish model, resources, and methods of determining growth factor and receptor function.

Animals↗

PubMed2004

Lipid metabolism in zebrafish.

Forward genetics is an unbiased methodology to discover new genes or functions of genes. At the present, the zebrafish is one of the few vertebrate systems where large-scale forward genetic studies are practical. Fluorescent lipid labeling of zebrafish larvae derived from families created from ENU-mutagenized fish enabled us to perform a large scale in vivo screen to identify mutants with perturbed lipid processing. With the aid of the zebrafish genome project, positional cloning of mutated genes with abnormal lipid metabolism can be accelerated. MO- and gripNA-based transient gene silencing is feasible in zebrafish embryos and provides a reverse genetic screening strategy to search for important lipid regulators. The advantages of using zebrafish as a vertebrate model to study lipid metabolism include its rapid external development and its optical clarity that enables the monitoring of biological processes. Large scale, high-throughput drug screening in vivo, especially for drugs that inhibit lipid absorption, can be easily achieved in this model. These zebrafish-based assays are important tools to understand aspects of lipid biology with significant clinical implications.

4-Chloro-7-nitrobenzofurazan↗

PubMed2001

Detailed immunohistology of Pax6 protein and tyrosine hydroxylase in the early zebrafish brain suggests role of Pax6 gene in development of dopaminergic diencephalic neurons.

Spatiotemporal developmental dynamics of Pax6 protein containing (i.e., Pax6) cells were investigated immunohistochemically in embryonic and postembryonic zebrafish brain sections (especially at 2 and 5 day), allowing for a neuroanatomically detailed resolution previously only reported for the mouse. Besides strikingly close correspondences of early Pax6 domains - including many spatiotemporal changes - in mouse and zebrafish brains, some critical differences were noted. There is no pallial (i.e., cortical) Pax6 expression domain in the ventricular proliferative layer in the zebrafish as in the mouse. The main pallial Pax6 domain in the zebrafish is comparable to the migrating stream of Pax6 cells at the pallial-subpallial boundary. This indicates that some developmental functions of Pax6 (i.e., inhibition of subpallial cell migration into pallium by Pax6 migrating stream) might be shared with the mouse and maybe all vertebrates, while others (i.e., control of intrapallial neuronal radial migration via Pax6 expressing radial glia cells) may be special for mammals. Another prominent feature in the early zebrafish forebrain is that the alar plate ventral thalamic Pax6 domain extends far caudolaterally into the periphery of the basal plate posterior tuberculum and hypothalamic inferior lobe. This indicates that the alar plate ventral thalamus invades the forebrain basal plate and contributes to the development of basal forebrain structures. The close spatiotemporal association of Pax6 cells and TH cells of the ventral thalamus indicates a local role of Pax6 in the development of ventral thalamic (as recently demonstrated in the mouse) and, maybe, posterior tubercular TH cells. However, our confocal microscopical analysis of zebrafish brain sections double-immunostained for Pax6 and TH did not reveal cells double-labeled for these two proteins in this location, but rather indicates an inductive interaction of Pax6 cells onto TH cells.

Animals↗

PubMed2003

Developmental estrogenic exposure in zebrafish (Danio rerio): II. Histological evaluation of gametogenesis and organ toxicity.

Aquatic species can be exposed to endocrine disrupting chemicals (EDCs) in wastewater that often includes the weak estrogen, 4-nonylphenol (NP) and the potent estrogen, 17alpha-ethinylestradiol (EE). The goal of the present study was to determine concentration-dependent effects of developmental exposure to NP and EE on gametogenesis, as well as gonad, kidney and liver pathology using quantitative histological evaluation of hematoxylin/eosin-stained saggital sections of zebrafish (Danio rerio). The major finding of the present study was that exposure to NP (>/=100 microg/l nominal) and EE (>/=1 ng/l nominal) from 2 to 60 days post-hatch (dph) caused concentration-dependent suppression of gametogenesis in both male and female zebrafish. Severe kidney pathology was observed in 60 dph zebrafish, specifically glomerular dilation or degeneration, fibrosis, tubule enlargement and tubule necrosis, at a threshold of 10 ng/l EE. However, minor kidney histopathology indicated by increased pyknotic nuclei in kidney tubule and interstitial (hematopoietic) cells was detected at lower estrogenic exposures (>/=10 microg/l NP nominal) than delayed gametogenesis. Considering all histological parameters in the current study, the rank order of potency for pathological effects in 60 dph zebrafish was 10 ng/l EE>1 ng/l EE=100 microg/l NP>30 microg/l NP>10 microg/l NP10 (nominal concentrations). Zebrafish from the same cohort examined in the current study that had been placed in clean water from 60 to 300 dph had histologically normal testes and no kidney or liver histopathology. However, increased ovarian follicle atresia was detected at 300 dph in zebrafish exposed developmentally to 100 microg/l NP. Therefore, we conclude that functional rather than morphological changes may be more important for future evaluations of developmental exposure to estrogens in fish, and that negative effects in female rather than male gonads may contribute to prolonged breeding impairment.

Animals↗

PubMed2002

Regulation of ornithine decarboxylase by antizymes and antizyme inhibitor in zebrafish (Danio rerio).

Mammalian polyamine synthesis is regulated by a unique feedback mechanism. When cellular polyamine levels increase, antizyme, an ornithine decarboxylase (ODC) inhibitory protein, is induced by polyamine-dependent translational frameshifting. Antizyme not only inhibits ODC, a key enzyme in polyamine synthesis, it also targets the enzyme degradation by the 26S proteasome. Furthermore, it suppresses cellular uptake of polyamines. Previously, we isolated two zebrafish antizymes with different expressions and activities. This suggested that a common feedback mechanism of polyamine metabolism might operate in mammals and zebrafish (Danio rerio). In the present study, cDNAs of zebrafish ODC and antizyme inhibitor, another regulatory protein that inhibits antizyme action, were cloned. The presence of ODC and antizyme inhibitor mRNAs was confirmed by Northern blotting in embryos and adult fish, as well as in a zebrafish-derived cell line (BRF41). The activity of the ODC cDNA expression product was inhibited by short and long zebrafish antizymes, and recombinant zebrafish antizyme inhibitor reversed this inhibition. In the BRF41 cells, the ODC half-life was considerably longer than that of mammalian ODC but shorter than that of Schizosaccharomyces pombe. Spermidine elicited a rapid decay of ODC activity and ODC protein in a protein synthesis-dependent manner.

Amino Acid Sequence↗

PubMed1998

Cloning and characterization of vascular endothelial growth factor (VEGF) from zebrafish, Danio rerio.

We have cloned and sequenced a zebrafish (Danio rerio) Vascular Endothelial Growth Factor (vegf) cDNA. It encodes a precursor protein of 188 amino acids with a putative 23 amino acids signal peptide. Sequence comparison analysis indicates that the zebrafish vegf cDNA corresponds to the human VEGF165 isoform and shows about 52% identity to human VEGF165 at the amino acid level. A 2.8 kb vegf message RNA was detected in adult zebrafish by Northern blot analysis. Expression of vegf165 is also detected by RT-PCR in adult fish and throughout the zebrafish embryonic development. Whole mount in situ hybridization of zebrafish embryos indicates strong expression in four areas of the 18-19 h post-fertilization (hpf) embryo: within the anterior central nervous system in the prospective optic stalk, in mesoderm overlapping the bilaterally located merging heart fields, in mesoderm underlying and flanking the hindbrain posterior to rhombomere 4, and in medial regions of the somites. The study of vegf function in zebrafish embryonic vascular development will contribute to our understanding of the mechanisms of vertebrate endothelial cell differentiation and vasculature formation.

Amino Acid Sequence↗