Gene Symbol: flt1
Description: fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)
Alias: VEGFR1, flt1b, sFlt1, vascular endothelial growth factor receptor 1, flt1a, receptor tyrosine kinase Flt1b, soluble fms-like tyrosine kinase 1
Species: zebrafish
Products:     flt1

Top Publications

  1. Krueger J, Liu D, Scholz K, Zimmer A, Shi Y, Klein C, et al. Flt1 acts as a negative regulator of tip cell formation and branching morphogenesis in the zebrafish embryo. Development. 2011;138:2111-20 pubmed publisher
    ..Zebrafish embryos expressed soluble Flt1 (sFlt1) and membrane-bound Flt1 (mFlt1)...
  2. Lam I, Alex D, Wang Y, Liu P, Liu A, Du G, et al. In vitro and in vivo structure and activity relationship analysis of polymethoxylated flavonoids: identifying sinensetin as a novel antiangiogenesis agent. Mol Nutr Food Res. 2012;56:945-56 pubmed publisher
    ..cell cycle arrest in the G0/G1 phase in HUVEC culture and downregulating the mRNA expressions of angiogenesis genes flt1, kdrl, and hras in zebrafish...
  3. Küchler A, Gjini E, Peterson Maduro J, Cancilla B, Wolburg H, Schulte Merker S. Development of the zebrafish lymphatic system requires VEGFC signaling. Curr Biol. 2006;16:1244-8 pubmed
  4. Tang J, Li S, Li Z, Zhang Z, Hu G, Cheang L, et al. Calycosin promotes angiogenesis involving estrogen receptor and mitogen-activated protein kinase (MAPK) signaling pathway in zebrafish and HUVEC. PLoS ONE. 2010;5:e11822 pubmed publisher
    ..HUVEC) in vitro and zebrafish embryos in vivo via the up-regulation of vascular endothelial growth factor (VEGF), VEGFR1 and VEGFR2 mRNA expression...
  5. Bussmann J, Bos F, Urasaki A, Kawakami K, Duckers H, Schulte Merker S. Arteries provide essential guidance cues for lymphatic endothelial cells in the zebrafish trunk. Development. 2010;137:2653-7 pubmed publisher
    ..In the absence of intersegmental arteries, LEC migration in the trunk is blocked. Our data therefore demonstrate a crucial role for arteries in LEC guidance. ..
  6. Bayliss P, Bellavance K, Whitehead G, Abrams J, Aegerter S, Robbins H, et al. Chemical modulation of receptor signaling inhibits regenerative angiogenesis in adult zebrafish. Nat Chem Biol. 2006;2:265-73 pubmed
    ..This study illustrates the utility of the adult zebrafish as a new model system for receptor signaling and chemical biology. ..
  7. Hu G, Mahady G, Li S, Hoi M, Wang Y, Lee S. Polysaccharides from astragali radix restore chemical-induced blood vessel loss in zebrafish. Vasc Cell. 2012;4:2 pubmed publisher
    ..These findings support the hypothesis that polysaccharides are one of the active constituents in Astragali Radix, contributing to its beneficial effect on treatment of diseases associated with a deficiency in angiogenesis. ..
  8. Li S, Lou S, Lei B, Chan T, Kwan Y, Chan S, et al. Transcriptional profiling of angiogenesis activities of calycosin in zebrafish. Mol Biosyst. 2011;7:3112-21 pubmed publisher
    ..The data have elucidated the connection between morphological observations and genomic evidence, indicating the potential roles of several key signaling pathways in angiogenesis. ..
  9. Rottbauer W, Just S, Wessels G, Trano N, Most P, Katus H, et al. VEGF-PLCgamma1 pathway controls cardiac contractility in the embryonic heart. Genes Dev. 2005;19:1624-34 pubmed
    ..Thus, the muscle of the heart uses the VEGF-PLCgamma1 cascade to control the strength of the heart beat. We speculate that this paracrine system may contribute to normal and pathological regulation of cardiac contractility. ..

More Information


  1. Hogan B, Bos F, Bussmann J, Witte M, Chi N, Duckers H, et al. Ccbe1 is required for embryonic lymphangiogenesis and venous sprouting. Nat Genet. 2009;41:396-8 pubmed publisher
    ..Ccbe1 acts at the same stage of development as Vegfc and is required for lymphangioblast budding and angiogenic sprouting from venous endothelium. ..
  2. Bower N, Vogrin A, Le Guen L, Chen H, Stacker S, Achen M, et al. Vegfd modulates both angiogenesis and lymphangiogenesis during zebrafish embryonic development. Development. 2017;144:507-518 pubmed publisher
    ..we find that vegfd and vegfc also redundantly drive artery hyperbranching phenotypes observed upon depletion of Flt1 or Dll4...
  3. Cermenati S, Moleri S, Cimbro S, Corti P, Del Giacco L, Amodeo R, et al. Sox18 and Sox7 play redundant roles in vascular development. Blood. 2008;111:2657-66 pubmed
    ..Our data suggest that a defect in arteriovenous identity could be responsible for the formation of telangiectases in patients with HLT. ..
  4. Zheng P, Severijnen L, van der Weiden M, Willemsen R, Kros J. A crucial role of caldesmon in vascular development in vivo. Cardiovasc Res. 2009;81:362-9 pubmed publisher
    ..Interfering with caldesmon opens new therapeutic avenues for anti-angiogenesis in cancer and ischaemic cardiovascular disease. ..
  5. Bussmann J, Wolfe S, Siekmann A. Arterial-venous network formation during brain vascularization involves hemodynamic regulation of chemokine signaling. Development. 2011;138:1717-26 pubmed publisher
  6. Renz M, Otten C, Faurobert E, Rudolph F, Zhu Y, Boulday G, et al. Regulation of β1 integrin-Klf2-mediated angiogenesis by CCM proteins. Dev Cell. 2015;32:181-90 pubmed publisher
    ..Our work reveals a β1 integrin-Klf2-Egfl7-signaling pathway that is tightly regulated by CCM proteins. This regulation prevents angiogenic overgrowth and ensures the quiescence of endothelial cells. ..
  7. Lam K, Alex D, Lam I, Tsui S, Yang Z, Lee S. Nobiletin, a polymethoxylated flavonoid from citrus, shows anti-angiogenic activity in a zebrafish in vivo model and HUVEC in vitro model. J Cell Biochem. 2011;112:3313-21 pubmed publisher
    ..This study, for the first time, identifies nobiletin as having potent anti-angiogenic activity and suggests that nobiletin has a great potential for future research and development as a cytostatic anti-proliferative agent. ..
  8. Jensen L, Nakamura M, Bräutigam L, Li X, Liu Y, Samani N, et al. VEGF-B-Neuropilin-1 signaling is spatiotemporally indispensable for vascular and neuronal development in zebrafish. Proc Natl Acad Sci U S A. 2015;112:E5944-53 pubmed publisher
    ..These findings show that VEGF-B is spatiotemporally required for vascular development in zebrafish embryos and that NRP1, but not VEGFR1, mediates the essential signaling.
  9. Avraham Davidi I, Ely Y, Pham V, Castranova D, Grunspan M, Malkinson G, et al. ApoB-containing lipoproteins regulate angiogenesis by modulating expression of VEGF receptor 1. Nat Med. 2012;18:967-73 pubmed publisher
    ..Mechanistically, we identified downregulation of vascular endothelial growth factor receptor 1 (VEGFR1), which acts as a decoy receptor for VEGF, as a key mediator of the endothelial ..
  10. Tu X, Deng Y, Chen J, Hu Q, He C, Jordan J, et al. Screening study on the anti-angiogenic effects of Traditional Chinese Medicine - Part I: Heat-clearing and detoxicating TCM. J Ethnopharmacol. 2016;194:280-287 pubmed publisher
    ..The results provide new insights into their clinical application and therapeutic potential for the management of angiogenesis-dependent diseases such as cancer. ..
  11. Helker C, Schuermann A, Karpanen T, Zeuschner D, Belting H, Affolter M, et al. The zebrafish common cardinal veins develop by a novel mechanism: lumen ensheathment. Development. 2013;140:2776-86 pubmed publisher
    ..Our findings not only identify a novel mechanism of vascular lumen formation, but also suggest a new form of developmental crosstalk between hematopoietic and endothelial cell lineages...
  12. Kuroyanagi J, Shimada Y, Zhang B, Ariyoshi M, Umemoto N, Nishimura Y, et al. Zinc finger MYND-type containing 8 promotes tumour angiogenesis via induction of vascular endothelial growth factor-A expression. FEBS Lett. 2014;588:3409-16 pubmed publisher
    ..Integrated analysis of human and zebrafish transcriptomes, which identified ZMYND8, might be a powerful strategy to determine also other molecular targets for inhibiting prostate cancer progression. ..
  13. Wang X, Ling C, Li L, Qin Y, Qi J, Liu X, et al. MicroRNA-10a/10b represses a novel target gene mib1 to regulate angiogenesis. Cardiovasc Res. 2016;110:140-50 pubmed publisher
    ..modulating the levels of membrane-bound fms-related tyrosine kinase 1 (mflt1) and its soluble splice isoform sflt1 post-transcriptionally in zebrafish...
  14. Sacilotto N, Monteiro R, Fritzsche M, Becker P, Sánchez del Campo L, Liu K, et al. Analysis of Dll4 regulation reveals a combinatorial role for Sox and Notch in arterial development. Proc Natl Acad Sci U S A. 2013;110:11893-8 pubmed publisher
    ..Fascinatingly, this combinatorial ablation leads to a loss of arterial markers and the absence of a detectable dorsal aorta, demonstrating the essential roles of SoxF and Notch, together, in the acquisition of arterial identity. ..
  15. Chappell J, Mouillesseaux K, Bautch V. Flt-1 (vascular endothelial growth factor receptor-1) is essential for the vascular endothelial growth factor-Notch feedback loop during angiogenesis. Arterioscler Thromb Vasc Biol. 2013;33:1952-9 pubmed publisher
    ..Elevated Notch signaling downstream of perturbed VEGF signaling contributes to aberrant flt-1(-/-) blood vessel formation. Notch signaling may be dispensable for blood vessel formation when VEGF signaling is below a critical threshold...
  16. Li S, Dang Y, Oi Lam Che G, Kwan Y, Chan S, Leung G, et al. VEGFR tyrosine kinase inhibitor II (VRI) induced vascular insufficiency in zebrafish as a model for studying vascular toxicity and vascular preservation. Toxicol Appl Pharmacol. 2014;280:408-20 pubmed publisher
    ..In addition, we showed that VRI-induced blood vessel loss in zebrafish represented a simple and effective in vivo model for studying vascular insufficiency and evaluating cancer drug vascular toxicities. ..
  17. Biyashev D, Veliceasa D, Topczewski J, Topczewska J, Mizgirev I, Vinokour E, et al. miR-27b controls venous specification and tip cell fate. Blood. 2012;119:2679-87 pubmed publisher
    ..and venous markers in human endothelium, including Ephrin B2 (EphB2), EphB4, FMS-related tyrosine kinase 1 (Flt1), and Flt4...
  18. Huang C, Huang C, Cheng Y, Yu J. Histamine metabolism influences blood vessel branching in zebrafish reg6 mutants. BMC Dev Biol. 2008;8:31 pubmed publisher
    ..Taken together, our results suggest that blood vessel branching is influenced by histamine metabolism, possibly through regulating the expression of the egr-1 transcription factor. ..
  19. Merrigan S, Kennedy B. Vitamin D receptor agonists regulate ocular developmental angiogenesis and modulate expression of dre-miR-21 and VEGF. Br J Pharmacol. 2017;174:2636-2651 pubmed publisher
    ..Interestingly, zebrafish ocular vegfaa and vegfab expression was significantly increased while, vegfc, flt1 and kdrl expression was unchanged by calcitriol...
  20. van Rooijen E, Voest E, Logister I, Bussmann J, Korving J, van Eeden F, et al. von Hippel-Lindau tumor suppressor mutants faithfully model pathological hypoxia-driven angiogenesis and vascular retinopathies in zebrafish. Dis Model Mech. 2010;3:343-53 pubmed publisher
    ..revealed increased expression of the duplicated VEGFA orthologs vegfaa and vegfab, and of vegfb and its receptors flt1, kdr and kdr-like, indicating increased vascular endothelial growth factor (Vegf) signaling in vhl mutants...
  21. Lai P, Chan J, Kwok H, Cheng L, Yu H, Lau C, et al. Induction of Angiogenesis in Zebrafish Embryos and Proliferation of Endothelial Cells by an Active Fraction Isolated from the Root of Astragalus membranaceus using Bioassay-guided Fractionation. J Tradit Complement Med. 2014;4:239-45 pubmed publisher
    ..A major AR active fraction consisting of glycoproteins was identified, and shown to promote angiogenesis in zebrafish embryos and proliferation of endothelial cells in vitro. ..
  22. Matsuoka R, Rossi A, Stone O, Stainier D. CNS-resident progenitors direct the vascularization of neighboring tissues. Proc Natl Acad Sci U S A. 2017;114:10137-10142 pubmed publisher
    ..Thus, our findings identify a critical function for CNS-resident progenitors in the regulation of vascularization outside the CNS, serving as a paradigm for cross-tissue coordination of vascular morphogenesis and growth. ..
  23. Chen J, He J, Li L, Yang D, Luo L. Cyp2aa9 regulates haematopoietic stem cell development in zebrafish. Sci Rep. 2016;6:26608 pubmed publisher
    ..Taken together, these data indicate that Cyp2aa9 is functional in the step of PGE2 synthesis from PGH2, thus promoting Wnt activation and definitive HSC development. ..
  24. Zhou Z, Huan L, Zhao W, Tang N, Jin Y, Tang J. Spatholobi Caulis extracts promote angiogenesis in HUVECs in vitro and in zebrafish embryos in vivo via up-regulation of VEGFRs. J Ethnopharmacol. 2017;200:74-83 pubmed publisher
    ..Thus, the current study provided evidence for the clinical usage of Spatholobi Caulis in promoting blood circulation and removing stasis in traditional Chinese medicine (TCM). ..
  25. Coxam B, Neyt C, Grassini D, Le Guen L, Smith K, Schulte Merker S, et al. carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase (cad) regulates Notch signaling and vascular development in zebrafish. Dev Dyn. 2015;244:1-9 pubmed publisher
    ..These findings suggest important posttranslational modifications requiring Cad as an unappreciated mechanism that regulates Notch/Vegf signaling during angiogenesis. ..
  26. Zygmunt T, Gay C, Blondelle J, Singh M, Flaherty K, Means P, et al. Semaphorin-PlexinD1 signaling limits angiogenic potential via the VEGF decoy receptor sFlt1. Dev Cell. 2011;21:301-14 pubmed publisher
    ..Specifically, Sema-PlxnD1 signaling ensures the proper endothelial abundance of soluble flt1 (sflt1), an alternatively spliced form of the VEGF receptor Flt1 encoding a potent secreted decoy...
  27. Hassel D, Cheng P, White M, Ivey K, Kroll J, Augustin H, et al. MicroRNA-10 regulates the angiogenic behavior of zebrafish and human endothelial cells by promoting vascular endothelial growth factor signaling. Circ Res. 2012;111:1421-33 pubmed publisher
    ..FLT1), a cell-surface protein that sequesters vascular endothelial growth factor, and its soluble splice variant sFLT1. The increase in FLT1/sFLT1 protein levels upon miR-10 knockdown in zebrafish and in human umbilical venous ..
  28. Bussmann J, Lawson N, Zon L, Schulte Merker S. Zebrafish VEGF receptors: a guideline to nomenclature. PLoS Genet. 2008;4:e1000064 pubmed publisher
  29. Chiang I, Fritzsche M, Pichol Thievend C, Neal A, Holmes K, Lagendijk A, et al. SoxF factors induce Notch1 expression via direct transcriptional regulation during early arterial development. Development. 2017;144:2629-2639 pubmed publisher
    ..These findings position SoxF transcription factors directly upstream of Notch receptor expression during the acquisition of arterial identity in vertebrates. ..
  30. Hashiura T, Kimura E, Fujisawa S, Oikawa S, Nonaka S, Kurosaka D, et al. Live imaging of primary ocular vasculature formation in zebrafish. PLoS ONE. 2017;12:e0176456 pubmed publisher
    ..Furthermore, this new morphological information enables us to assess the entire process of the primary ocular vasculature formation, which will be useful for its precise understanding. ..
  31. Fukuda M, Ohtani K, Jang S, Yoshizaki T, Mori K, Motomura W, et al. Molecular cloning and functional analysis of scavenger receptor zebrafish CL-P1. Biochim Biophys Acta. 2011;1810:1150-9 pubmed publisher
    ..These results suggest that zCL-P1 might be essential for vasculogenesis during the early embryonic phase in bone fish. ..
  32. Rossi A, Gauvrit S, Marass M, Pan L, Moens C, Stainier D. Regulation of Vegf signaling by natural and synthetic ligands. Blood. 2016;128:2359-2366 pubmed publisher
    ..Taking advantage of a new vegfr1 tyrosine kinase-deficient mutant, we determined that Pgfb rescues vegfaa mutants via Vegfr1...
  33. Ba Q, Duan J, Tian J, Wang Z, Chen T, Li X, et al. Dihydroartemisinin promotes angiogenesis during the early embryonic development of zebrafish. Acta Pharmacol Sin. 2013;34:1101-7 pubmed publisher
    ..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...
  34. Ando K, Fukuhara S, Izumi N, Nakajima H, Fukui H, Kelsh R, et al. Clarification of mural cell coverage of vascular endothelial cells by live imaging of zebrafish. Development. 2016;143:1328-39 pubmed publisher
    ..Thus, live imaging and lineage tracing enabled us to clarify precisely how MCs cover the EC tubes and to identify the origins of MCs. ..
  35. Cobbina S, Xu H, Zhao T, Mao G, Zhou Z, Wu X, et al. A multivariate assessment of innate immune-related gene expressions due to exposure to low concentration individual and mixtures of four kinds of heavy metals on zebrafish (Danio rerio) embryos. Fish Shellfish Immunol. 2015;47:1032-42 pubmed publisher
    ..It is indicative that mechanisms associated with toxicity of metal mixtures is complex, however, further studies to elucidate them are ongoing in our research laboratory. ..
  36. Zhang Z, Li J, Li S, Liu A, Hoi P, Tian H, et al. In vivo angiogenesis screening and mechanism of action of novel tanshinone derivatives produced by one-pot combinatorial modification of natural tanshinone mixture from Salvia miltiorrhiza. PLoS ONE. 2014;9:e100416 pubmed publisher
    ..Our results highlighted the great potential of adopting a newly modified one-pot approach to enhance the chemical diversity and biological activities of constituents from natural products regardless of their abundances. ..
  37. Matsuoka R, Marass M, Avdesh A, Helker C, Maischein H, Grosse A, et al. Radial glia regulate vascular patterning around the developing spinal cord. elife. 2016;5: pubmed publisher
    ..Mechanistically, we determined that radial glia control this process via the Vegf decoy receptor sFlt1: sflt1 mutants exhibit the venous over-sprouting observed in radial glia-ablated larvae, and sFlt1 ..
  38. Tonon F, Zennaro C, Dapas B, Carraro M, Mariotti M, Grassi G. Rapid and cost-effective xenograft hepatocellular carcinoma model in Zebrafish for drug testing. Int J Pharm. 2016;515:583-591 pubmed publisher
    ..In conclusion, the possibility to test anti HCC/neo-angiogenesis drugs makes our JHH6 model useful to select therapeutic molecules for a highly vascularized tumor such as HCC. ..
  39. Li S, Dang Y, Zhou X, Huang B, Huang X, Zhang Z, et al. Formononetin promotes angiogenesis through the estrogen receptor alpha-enhanced ROCK pathway. Sci Rep. 2015;5:16815 pubmed publisher
  40. Wild R, Klems A, Takamiya M, Hayashi Y, Strahle U, Ando K, et al. Neuronal sFlt1 and Vegfaa determine venous sprouting and spinal cord vascularization. Nat Commun. 2017;8:13991 pubmed publisher
    ..zebrafish spinal cord neurons coordinate vessel growth through balancing of neuron-derived Vegfaa, with neuronal sFlt1 restricting Vegfaa-Kdrl mediated angiogenesis at the neurovascular interface...
  41. Kaufman R, Weiss O, Sebbagh M, Ravid R, Gibbs Bar L, Yaniv K, et al. Development and origins of zebrafish ocular vasculature. BMC Dev Biol. 2015;15:18 pubmed publisher
    ..Our results provide a thorough analysis of the early development and origins of zebrafish ocular vessels and establish the superficial vasculature as a model for studying vascular patterning in the context of the developing eye. ..
  42. Li S, Zhou X, Dang Y, Kwan Y, Chan S, Leung G, et al. Basal Flt1 tyrosine kinase activity is a positive regulator of endothelial survival and vascularization during zebrafish embryogenesis. Biochim Biophys Acta. 2015;1850:373-84 pubmed publisher
    ..The effects of VEGFR1/2 kinase inhibitor (VRI) and calycosin on Flt1 tyrosine kinase (TK) activity were evaluated by molecular docking, ..
  43. Kwon H, Fukuhara S, Asakawa K, Ando K, Kashiwada T, Kawakami K, et al. The parallel growth of motoneuron axons with the dorsal aorta depends on Vegfc/Vegfr3 signaling in zebrafish. Development. 2013;140:4081-90 pubmed publisher
    ..Finally, a vegfr3 mutant fish lacked the motoneuron axons beneath the DA. Collectively, Vegfc from the preformed DA guides the axon growth of secondary motoneurons. ..
  44. Marín Juez R, Marass M, Gauvrit S, Rossi A, Lai S, Materna S, et al. Fast revascularization of the injured area is essential to support zebrafish heart regeneration. Proc Natl Acad Sci U S A. 2016;113:11237-11242 pubmed
    ..Our work also paves the way for future studies designed to understand the molecular mechanisms that regulate fast revascularization. ..
  45. Fan Z, Wang D, Yang J, Lin Z, Lin Y, Yang A, et al. Dalbergia odorifera extract promotes angiogenesis through upregulation of VEGFRs and PI3K/MAPK signaling pathways. J Ethnopharmacol. 2017;204:132-141 pubmed publisher
    ..These results suggest a strong potential for Dalbergia odorifera to be developed as an angiogenesis-promoting therapeutic. ..
  46. Wang Y, Pan L, Moens C, Appel B. Notch3 establishes brain vascular integrity by regulating pericyte number. Development. 2014;141:307-17 pubmed publisher
    ..These findings establish a new role for Notch signaling in brain vascular development whereby Notch3 signaling promotes expansion of the brain pericyte population. ..