Vascular Endothelial Growth Factor and Its Receptors in Embryonic Zebrafish Blood Vessel Development

Goishi, Katsutoshi; Klagsbrun, Michael

doi:10.1016/s0070-2153(04)62005-9

Cited by 32 publications

(24 citation statements)

References 159 publications

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“…In zebrafish, flk1 has an essential role in vasculogenesis, angiogenesis and hematopoiesis, which can mediate vascular dilation, endothelial cell proliferation and epidermal hyperplasia by binding VEGF [25] . In our studies, the knockdown of flk1 with antisense MOs blocked the pericardial edema phenotype, which confirmed that DHA exerted its effects through the VEGF-flk1 pathway.…”

Section: Discussionmentioning

confidence: 99%

Dihydroartemisinin promotes angiogenesis during the early embryonic development of zebrafish

Duan

Tian

et al. 2013

Acta Pharmacol Sin

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Aim: To investigate the embryotoxicity of dihydroartemisinin (DHA), the main active metabolite of artemisinin, in zebrafish, and explore the corresponding mechanisms. Methods: The embryos of wild type and TG (flk1:GFP) transgenic zebrafish were exposed to DHA. Developmental phenotypes of the embryos were observed. Development of blood vessels was directly observed in living embryos of TG (flk1:GFP) transgenic zebrafish under fluorescence microscope. The expression of angiogenesis marker genes vegfa, flk1, and flt1 in the embryos was detected using real-time PCR and RNA in situ hybridization assays. Results: Exposure to DHA (1-10 mg/L) dose-dependently caused abnormal zebrafish embryonic phenotypes in the early developmental stage. Furthermore, exposure to DHA (10 mg/L) resulted in more pronounced embryonic angiogenesis in TG (flk1:GFP) zebrafish line. Exposure to DHA (10 mg/L) significantly increased the mRNA expression of vegfa, flk1, and flt1 in the embryos. Knockdown of the flk1 protein partially blocked the effects of DHA on embryogenesis. Conclusion: DHA causes abnormal embryonic phenotypes and promotes angiogenesis in zebrafish early embryonic development, demonstrating the potential embryotoxicity of DHA.

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Section: Discussionmentioning

confidence: 99%

Dihydroartemisinin promotes angiogenesis during the early embryonic development of zebrafish

Duan

Tian

et al. 2013

Acta Pharmacol Sin

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“…17 Zebrafish have proven useful for dissecting vascular developmental pathways. 18 A single zebrafish vegfA gene has been previously described, encoding the 121-and 165-aa isoforms. 19,20 Although VegfA 121 is the predominant isoform in early embryos and VegfA 165 in adults, other alternate transcripts exist in specific tissues.…”

Section: Introductionmentioning

confidence: 99%

Duplicate VegfA genes and orthologues of the KDR receptor tyrosine kinase family mediate vascular development in the zebrafish

Bahary

Goishi

Stuckenholz

et al. 2007

Blood

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Vascular endothelial growth factor A (VEGFA) and the type III receptor tyrosine kinase receptors (RTKs) are both required for the differentiation of endothelial cells (vasculogenesis) and for the sprouting of new capillaries (angiogenesis). We have isolated a duplicated zebrafish VegfA locus, termed VegfAb, and a duplicate RTK locus with homology to KDR/FLK1 (named Kdrb). Morpholinodisrupted VegfAb embryos develop a normal circulatory system until approximately 2 to 3 days after fertilization (dpf), when defects in angiogenesis permit blood to extravasate into many tissues. Unlike the VegfAa 121 and VegfAa 165 isoforms, the VegfAb isoforms VegfAb 171 IntroductionDifferentiation of endothelial cells to form the vascular network of arteries and veins requires a critical mitogenic signal, vascular endothelial growth factor A (VEGFA), which is transduced to the nucleus through a number of functionally redundant receptors. These receptors include the type III receptor tyrosine kinases VEGFR1/FLT1, VEGFR2/FLK1 (human KDR), and type I nonkinase transmembrane receptors neuropilin 1 (NRP1) and NRP2, 1 which are critical mediators of both vasculogenesis (de novo formation of blood vessels) and angiogenesis (sprouting of vessels from preexisting vessels). 2 Mice hemizygous at their single VegfA locus show defective vasculogenesis and die between 11 and 12 days after conception (dpc). [3][4][5] Embryos homozygous for a targeted disruption of Flk1 (Vegfr2) die between 8.5 and 9.5 dpc from defects in both hematopoiesis and vasculogenesis, but disruption of Flt1 (Vegfr1) only leads to perturbed vascular patterning in full-term embryos. 6,7 The tight regulation of VEGFA levels and the requirement for its receptors in hematopoiesis and vasculogenesis point to its critical role in the formation of blood vessels during development.Differential splicing of the single VEGFA locus in humans gives rise to multiple protein isoforms, ranging in size from 121 to 206 amino acids (aa's) (VEGFA 121 , VEGFA 145 , VEGFA 165 , VEGFA 189 , and VEGF 206 ). 8,9 The VEGF isoforms differ mainly by the presence or absence of 2 heparin-binding domains encoded within exon 6 and 7 sequences. [10][11][12] Expression of a single VEGFA isoform rescues VegfA mutant mice through birth, although the vascular networks differ with expression of different isoforms. [13][14][15][16] VEGFA splicing is regulated during development and in disease, resulting in tissue-and stage-specific isoform ratios, which allow for distinct, context-dependent VEGFA signaling. 17 Zebrafish have proven useful for dissecting vascular developmental pathways. 18 A single zebrafish vegfA gene has been previously described, encoding the 121-and 165-aa isoforms. 19,20 Although VegfA 121 is the predominant isoform in early embryos and VegfA 165 in adults, other alternate transcripts exist in specific tissues. 21 The initial establishment of axial vasculature patterning does not require VegfA, but the sprouting of intersegmental vessels does. 22 Together, these results show that VegfA...

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“…NRP2 mutant mice show abnormal development of small lymphatic vessels and capillaries, suggesting a selective role for NRP2 in lymphatic vessel development (13). In zebrafish embryos, NRP1 knockdown with morpholinos results in loss of the angiogenic intersegmental vessels (19,20).…”

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confidence: 99%

Site-directed Mutagenesis in the B-Neuropilin-2 Domain Selectively Enhances Its Affinity to VEGF165, but Not to Semaphorin 3F

Geretti

Shimizu

Kurschat

et al. 2007

Journal of Biological Chemistry

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Vascular Endothelial Growth Factor and Its Receptors in Embryonic Zebrafish Blood Vessel Development

Cited by 32 publications

References 159 publications

Dihydroartemisinin promotes angiogenesis during the early embryonic development of zebrafish

Dihydroartemisinin promotes angiogenesis during the early embryonic development of zebrafish

Duplicate VegfA genes and orthologues of the KDR receptor tyrosine kinase family mediate vascular development in the zebrafish

Site-directed Mutagenesis in the B-Neuropilin-2 Domain Selectively Enhances Its Affinity to VEGF165, but Not to Semaphorin 3F

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