Gene Symbol: flt4
Description: fms-related tyrosine kinase 4
Alias: VEGFR3, cb1059, vascular endothelial growth factor receptor 3, expando, receptor tyrosine kinase Flt4
Species: zebrafish
Products:     flt4

Top Publications

  1. Wiley D, Kim J, Hao J, Hong C, Bautch V, Jin S. Distinct signalling pathways regulate sprouting angiogenesis from the dorsal aorta and the axial vein. Nat Cell Biol. 2011;13:686-92 pubmed publisher
  2. Chan J, Bayliss P, Wood J, Roberts T. Dissection of angiogenic signaling in zebrafish using a chemical genetic approach. Cancer Cell. 2002;1:257-67 pubmed
    ..This approach allowed us to examine the effects of blood flow and the role of endothelial signals in organogenesis. ..
  3. 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. ..
  4. 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. ..
  5. Jin S, Beis D, Mitchell T, Chen J, Stainier D. Cellular and molecular analyses of vascular tube and lumen formation in zebrafish. Development. 2005;132:5199-209 pubmed
    ..These studies provide the tools and a cellular framework for the investigation of mutations affecting vasculogenesis in zebrafish. ..
  6. Torres Vazquez J, Kamei M, Weinstein B. Molecular distinction between arteries and veins. Cell Tissue Res. 2003;314:43-59 pubmed
    ..Here we review some of the molecular mechanisms involved in this process. ..
  7. 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. ..
  8. Ober E, Olofsson B, Makinen T, Jin S, Shoji W, Koh G, et al. Vegfc is required for vascular development and endoderm morphogenesis in zebrafish. EMBO Rep. 2004;5:78-84 pubmed
  9. Zhu C, Smith T, MCNULTY J, Rayla A, Lakshmanan A, Siekmann A, et al. Evaluation and application of modularly assembled zinc-finger nucleases in zebrafish. Development. 2011;138:4555-64 pubmed publisher
    ..This work provides a resource to allow targeted germline gene inactivation in zebrafish and highlights the benefit of a definitive reverse genetic strategy to reveal gene function. ..

More Information


  1. Nicoli S, Knyphausen C, Zhu L, Lakshmanan A, Lawson N. miR-221 is required for endothelial tip cell behaviors during vascular development. Dev Cell. 2012;22:418-29 pubmed publisher
    ..miR-221 knockdown phenocopied defects associated with loss of the tip cell-expressed Flt4 receptor...
  2. Geudens I, Herpers R, Hermans K, Segura I, Ruiz de Almodovar C, Bussmann J, et al. Role of delta-like-4/Notch in the formation and wiring of the lymphatic network in zebrafish. Arterioscler Thromb Vasc Biol. 2010;30:1695-702 pubmed publisher
    ..At a later phase, Notch silencing impaired navigation of lymphatic intersomitic vessels along their arterial templates. These studies imply critical roles for Notch signaling in the formation and wiring of the lymphatic network. ..
  3. Siekmann A, Lawson N. Notch signalling limits angiogenic cell behaviour in developing zebrafish arteries. Nature. 2007;445:781-4 pubmed
    ..Furthermore, we find that flt4 (fms-related tyrosine kinase 4, also called vegfr3) is expressed in segmental artery tip cells and becomes ectopically expressed throughout the sprout in the absence ..
  4. 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
    ..distinct from blood vessels and show that the development of these vessels depends on Vegfc and VEGFR-3/Flt4 signaling...
  5. Sumanas S, Lin S. Ets1-related protein is a key regulator of vasculogenesis in zebrafish. PLoS Biol. 2006;4:e10 pubmed
    ..These results demonstrate that Etsrp is necessary and sufficient for the initiation of vasculogenesis. ..
  6. Okuda K, Astin J, Misa J, Flores M, Crosier K, Crosier P. lyve1 expression reveals novel lymphatic vessels and new mechanisms for lymphatic vessel development in zebrafish. Development. 2012;139:2381-91 pubmed publisher
    ..Our work highlights the additional complexity of lymphatic vessel development in the zebrafish that may increase its versatility as a model of lymphangiogenesis. ..
  7. 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
    ..Importantly, they will allow for a cost-effective, non-invasive and efficient way to screen for novel pharmacological agents and combinatorial treatments. ..
  8. Covassin L, Villefranc J, Kacergis M, Weinstein B, Lawson N. Distinct genetic interactions between multiple Vegf receptors are required for development of different blood vessel types in zebrafish. Proc Natl Acad Sci U S A. 2006;103:6554-9 pubmed
    ..We further find that Flt4, a receptor for Vegfc, cooperates with Kdr during artery morphogenesis, but not differentiation...
  9. Siegel N, Hoegg S, Salzburger W, Braasch I, Meyer A. Comparative genomics of ParaHox clusters of teleost fishes: gene cluster breakup and the retention of gene sets following whole genome duplications. BMC Genomics. 2007;8:312 pubmed
  10. Lamont R, Vu W, Carter A, Serluca F, Macrae C, Childs S. Hedgehog signaling via angiopoietin1 is required for developmental vascular stability. Mech Dev. 2010;127:159-68 pubmed publisher
    ..This is the first direct in vivo link between hedgehog signaling and the induction of vascular stability by recruitment of perivascular mural cells through angiopoietin signaling. ..
  11. Skarie J, Link B. FoxC1 is essential for vascular basement membrane integrity and hyaloid vessel morphogenesis. Invest Ophthalmol Vis Sci. 2009;50:5026-34 pubmed publisher
    ..Genetic interactions between FOXC1 and basement membrane components influence vascular stability and may impact glaucoma development and increase stroke risk in FOXC1 patients. ..
  12. Gering M, Yamada Y, Rabbitts T, Patient R. Lmo2 and Scl/Tal1 convert non-axial mesoderm into haemangioblasts which differentiate into endothelial cells in the absence of Gata1. Development. 2003;130:6187-99 pubmed
    ..These results suggest that, in the absence of inducers of erythroid or myeloid haematopoiesis, Scl/Tal1-Lmo2-induced haemangioblasts differentiate into endothelial cells. ..
  13. 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
    ..These findings may open new avenues for the treatment of lipoprotein-related vascular disorders. ..
  14. 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
    ..showed reduced expression of Notch receptors and of the Notch downstream target efnb2a, and ectopic expression of flt4 in arteries, consistent with loss of Notch signaling...
  15. 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
    ..Hence, Sema-PlxnD1 signaling regulates distinct but related aspects of angiogenesis: the spatial allocation of angiogenic capacity within a primary vessel and sprout guidance. ..
  16. van Impel A, Zhao Z, Hermkens D, Roukens M, Fischer J, Peterson Maduro J, et al. Divergence of zebrafish and mouse lymphatic cell fate specification pathways. Development. 2014;141:1228-38 pubmed publisher
    ..Together, these findings suggest that lymphatic commitment in zebrafish and mice is controlled in fundamentally different ways. ..
  17. Herbert S, Huisken J, Kim T, Feldman M, Houseman B, Wang R, et al. Arterial-venous segregation by selective cell sprouting: an alternative mode of blood vessel formation. Science. 2009;326:294-8 pubmed publisher
    ..Thus, directional control of progenitor migration drives arterial-venous segregation and generation of separate parallel vessels from a single precursor vessel, a process essential for vascular development. ..
  18. Williams C, Kim S, Ni T, Mitchell L, Ro H, Penn J, et al. Hedgehog signaling induces arterial endothelial cell formation by repressing venous cell fate. Dev Biol. 2010;341:196-204 pubmed publisher
    ..Collectively, these studies suggest that arterial endothelial cells are specified and formed via repressing venous cell fate at the lateral plate mesoderm by Hh signaling during vasculogenesis. ..
  19. Hogan B, Herpers R, Witte M, Helotera H, Alitalo K, Duckers H, et al. Vegfc/Flt4 signalling is suppressed by Dll4 in developing zebrafish intersegmental arteries. Development. 2009;136:4001-9 pubmed publisher
    ..governing vessel formation in vivo, we performed a forward genetic screen in zebrafish and isolated the mutant expando. Molecular characterisation revealed a loss-of-function mutation in the highly conserved kinase insert region of ..
  20. Aranguren X, Beerens M, Vandevelde W, Dewerchin M, Carmeliet P, Luttun A. Transcription factor COUP-TFII is indispensable for venous and lymphatic development in zebrafish and Xenopus laevis. Biochem Biophys Res Commun. 2011;410:121-6 pubmed publisher
    ..Therefore, the role of NR2F2 in EC fate determination is evolutionary conserved...
  21. Fujita M, Cha Y, Pham V, Sakurai A, Roman B, Gutkind J, et al. Assembly and patterning of the vascular network of the vertebrate hindbrain. Development. 2011;138:1705-15 pubmed publisher
    ..Knockdown of either cxcl12b or cxcr4a results in defects in basilar artery formation, showing that the assembly and patterning of this crucial artery depends on chemokine signaling. ..
  22. Lawson N, Vogel A, Weinstein B. sonic hedgehog and vascular endothelial growth factor act upstream of the Notch pathway during arterial endothelial differentiation. Dev Cell. 2002;3:127-36 pubmed
    ..These studies reveal a complex signaling cascade responsible for establishing arterial cell fate and suggest differential effects of Vegf on developing endothelial cells. ..
  23. 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
  24. North T, Goessling W, Peeters M, Li P, Ceol C, Lord A, et al. Hematopoietic stem cell development is dependent on blood flow. Cell. 2009;137:736-48 pubmed publisher
    ..This work links blood flow to AGM hematopoiesis and identifies NO as a conserved downstream regulator of HSC development. ..
  25. Villefranc J, Nicoli S, Bentley K, Jeltsch M, Zarkada G, Moore J, et al. A truncation allele in vascular endothelial growth factor c reveals distinct modes of signaling during lymphatic and vascular development. Development. 2013;140:1497-506 pubmed publisher
    ..truncated Vegfc, blocking its secretion and paracrine activity but not its ability to activate its receptor Flt4. When expressed in endothelial cells, vegfc(um18) could not rescue lymphatic defects in mutant embryos, but induced ..
  26. Perens E, Garavito Aguilar Z, Guio Vega G, Peña K, Schindler Y, Yelon D. Hand2 inhibits kidney specification while promoting vein formation within the posterior mesoderm. elife. 2016;5: pubmed publisher
    ..Together, our data suggest that hand2 functions in opposition to osr1 to balance the formation of kidney and vein progenitors by regulating cell fate decisions at the lateral boundary of the IM. ..
  27. 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. ..
  28. Pham V, Lawson N, Mugford J, Dye L, Castranova D, Lo B, et al. Combinatorial function of ETS transcription factors in the developing vasculature. Dev Biol. 2007;303:772-83 pubmed
    ..Our results demonstrate that combinatorial ETS factor function is essential for early endothelial specification and differentiation. ..
  29. Mei J, Liu S, Li Z, Gui J. Mtmr8 is essential for vasculature development in zebrafish embryos. BMC Dev Biol. 2010;10:96 pubmed publisher
    ..Here, we attempt to explore the function of Mtmr8 in vasculature development parallel to its function in muscle development...
  30. Astin J, Haggerty M, Okuda K, Le Guen L, Misa J, Tromp A, et al. Vegfd can compensate for loss of Vegfc in zebrafish facial lymphatic sprouting. Development. 2014;141:2680-90 pubmed publisher
    ..b>Vegfr3 signalling, through its ligand Vegfc and the extracellular protein Ccbe1, is essential for the sprouting of LECs ..
  31. Wilkinson R, Koudijs M, Patient R, Ingham P, Schulte Merker S, van Eeden F. Hedgehog signaling via a calcitonin receptor-like receptor can induce arterial differentiation independently of VEGF signaling in zebrafish. Blood. 2012;120:477-88 pubmed publisher
    ..Finally, our experiments establish a dual function of Hh during induction of runx1(+) HSCs. ..
  32. Jin S, Herzog W, Santoro M, Mitchell T, Frantsve J, Jungblut B, et al. A transgene-assisted genetic screen identifies essential regulators of vascular development in vertebrate embryos. Dev Biol. 2007;307:29-42 pubmed
    ..The analysis of the newly defined loci should lead to a greater understanding of vascular development and possibly provide new drug targets to treat the numerous pathologies associated with dysregulated blood vessel growth. ..
  33. Jin D, Zhu D, Fang Y, Chen Y, Yu G, Pan W, et al. Vegfa signaling regulates diverse artery/vein formation in vertebrate vasculatures. J Genet Genomics. 2017;44:483-492 pubmed publisher
    ..These findings suggest that Vegfa signaling governs the formation of diverse arteries/veins by distinct cellular mechanisms in vertebrate vasculatures. ..
  34. Ernens I, Lumley A, Zhang L, Devaux Y, Wagner D. Hypoxia inhibits lymphatic thoracic duct formation in zebrafish. Biochem Biophys Res Commun. 2017;482:1129-1134 pubmed publisher
    ..In conclusion, hypoxia has opposite effects on vascular development in zebrafish, inhibiting the development of the lymphatic vascular system while promoting the development of the blood vascular system. ..
  35. Hirashima M, Suda T. Differentiation of arterial and venous endothelial cells and vascular morphogenesis. Endothelium. 2006;13:137-45 pubmed
    ..These insights indicate that the balance of these genetic factors and modification by epigenetic factors such as hemodynamics and oxygen tension are important for proper endothelial cell identities in vascular morphogenesis. ..
  36. Rissone A, Foglia E, Sangiorgio L, Cermenati S, Nicoli S, Cimbro S, et al. The synaptic proteins ?-neurexin and neuroligin synergize with extracellular matrix-binding vascular endothelial growth factor a during zebrafish vascular development. Arterioscler Thromb Vasc Biol. 2012;32:1563-72 pubmed publisher
    ..Our data represent the first in vivo evidence of the role of neurexin and neuroligin in embryonic blood vessel formation and provide insights into their mechanism of action. ..
  37. Hermkens D, van Impel A, Urasaki A, Bussmann J, Duckers H, Schulte Merker S. Sox7 controls arterial specification in conjunction with hey2 and efnb2 function. Development. 2015;142:1695-704 pubmed publisher
    ..In situ hybridization and live observations in flt4:mCitrine transgenic embryos revealed increased expression levels of flt4 in arterial endothelial cells at the exact ..
  38. Baeyens N, Nicoli S, Coon B, Ross T, van den Dries K, Han J, et al. Vascular remodeling is governed by a VEGFR3-dependent fluid shear stress set point. elife. 2015;4: pubmed publisher
    ..b>VEGFR3 levels, a component of a junctional mechanosensory complex, mediate these differences...
  39. Rost M, Sumanas S. Hyaluronic acid receptor Stabilin-2 regulates Erk phosphorylation and arterial--venous differentiation in zebrafish. PLoS ONE. 2014;9:e88614 pubmed publisher
    ..These results argue that Stab2 is involved in a novel signaling pathway that plays an important role in regulating Erk phosphorylation and establishing arterial-venous identity...
  40. Le Guen L, Karpanen T, Schulte D, Harris N, Koltowska K, Roukens G, et al. Ccbe1 regulates Vegfc-mediated induction of Vegfr3 signaling during embryonic lymphangiogenesis. Development. 2014;141:1239-49 pubmed publisher
    The VEGFC/VEGFR3 signaling pathway is essential for lymphangiogenesis (the formation of lymphatic vessels from pre-existing vasculature) during embryonic development, tissue regeneration and tumor progression...
  41. Chen X, Gays D, Milia C, Santoro M. Cilia Control Vascular Mural Cell Recruitment in Vertebrates. Cell Rep. 2017;18:1033-1047 pubmed publisher
    ..In summary, we have identified a hemodynamic-dependent mechanism in the developing vasculature that controls vMC recruitment. ..
  42. 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. ..
  43. 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. ..
  44. 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
  45. 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. ..
  46. Fang L, Choi S, Baek J, Liu C, Almazan F, Ulrich F, et al. Control of angiogenesis by AIBP-mediated cholesterol efflux. Nature. 2013;498:118-22 pubmed publisher
    ..Our findings demonstrate that secreted AIBP positively regulates cholesterol efflux from endothelial cells and that effective cholesterol efflux is critical for proper angiogenesis...
  47. Becker P, Sacilotto N, Nornes S, Neal A, Thomas M, Liu K, et al. An Intronic Flk1 Enhancer Directs Arterial-Specific Expression via RBPJ-Mediated Venous Repression. Arterioscler Thromb Vasc Biol. 2016;36:1209-19 pubmed publisher
  48. Fish J, Cantu Gutierrez M, Dang L, Khyzha N, Chen Z, Veitch S, et al. Dynamic regulation of VEGF-inducible genes by an ERK/ERG/p300 transcriptional network. Development. 2017;144:2428-2444 pubmed publisher
    ..Collectively, these findings elucidate a novel transcriptional pathway contributing to VEGF-dependent angiogenesis. ..
  49. Chun C, Kaur S, Samant G, Wang L, Pramanik K, Garnaas M, et al. Snrk-1 is involved in multiple steps of angioblast development and acts via notch signaling pathway in artery-vein specification in vertebrates. Blood. 2009;113:1192-9 pubmed publisher
    ..The snrk-1 gene acts downstream or parallel to notch and upstream of gridlock during artery-vein specification, and the human gene compensates for zebrafish snrk-1 knockdown, suggesting evolutionary conservation of function. ..
  50. Cermenati S, Moleri S, Neyt C, Bresciani E, Carra S, Grassini D, et al. Sox18 genetically interacts with VegfC to regulate lymphangiogenesis in zebrafish. Arterioscler Thromb Vasc Biol. 2013;33:1238-47 pubmed publisher
    ..We addressed this issue in zebrafish. Mutations in the transcription factor-coding gene SOX18 and in VEGFR3 cause lymphedema, and the VEGFR3/Flt4 ligand VEGFC plays an evolutionarily conserved role in lymphangiogenesis...
  51. Yan H, Zhang C, Wang Z, Tu T, Duan H, Luo Y, et al. CD146 is required for VEGF-C-induced lymphatic sprouting during lymphangiogenesis. Sci Rep. 2017;7:7442 pubmed publisher
    ..Altogether, our data reveals a critical role of CD146 to mediate VEGF-C signaling pathway in lymphangiogenesis. ..
  52. Gupta A, Hall V, Kok F, Shin M, McNulty J, Lawson N, et al. Targeted chromosomal deletions and inversions in zebrafish. Genome Res. 2013;23:1008-17 pubmed publisher
    ..The ability to efficiently delete genomic segments in a vertebrate developmental system will facilitate the study of functional noncoding elements on an organismic level...
  53. Wu B, Chiu C, Chen C, Wang W, Wang J, Wen Z, et al. Nuclear receptor subfamily 2 group F member 1a (nr2f1a) is required for vascular development in zebrafish. PLoS ONE. 2014;9:e105939 pubmed publisher
    ..We found that a loss of nr2f1a results in a decreased expression of vein/ISV specific markers, flt4, mrc1, vascular markers stabilin and ephrinb2...
  54. Chen D, Li L, Tu X, Yin Z, Wang Q. Functional characterization of Klippel-Trenaunay syndrome gene AGGF1 identifies a novel angiogenic signaling pathway for specification of vein differentiation and angiogenesis during embryogenesis. Hum Mol Genet. 2013;22:963-76 pubmed publisher
    ..Overexpression of AGGF1 increased expression of venous markers (e.g. flt4), but had little effect on arterial markers (e.g. notch5)...
  55. 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. ..
  56. Liu L, Lin M, Lai Z, Jiang J, Huang Y, Jao L, et al. Motor neuron-derived Thsd7a is essential for zebrafish vascular development via the Notch-dll4 signaling pathway. J Biomed Sci. 2016;23:59 pubmed publisher
    ..Thsd7a could regulate ISV angiogenesis via Notch-dll4 signaling. Thus, Thsd7a is a potent angioneurin involved in the development of both neural and vascular systems. ..
  57. Huang H, Jin T, Wang L, Wang F, Zhang R, Pan Y, et al. The RAS guanyl nucleotide-releasing protein RasGRP1 is involved in lymphatic development in zebrafish. J Biol Chem. 2013;288:2355-64 pubmed publisher
    ..Further analysis revealed that RasGRP1 knockdown could synergize with flt4/vegfr3 knockdown to induce defects in lymphangiogenesis...
  58. Arduini B, Henion P. Melanophore sublineage-specific requirement for zebrafish touchtone during neural crest development. Mech Dev. 2004;121:1353-64 pubmed
    ..Further, our results suggest that, like other neural crest-derived sublineages, melanogenic precursors constitute a heterogeneous population with respect to genetic requirements for development...
  59. Goi M, Childs S. Patterning mechanisms of the sub-intestinal venous plexus in zebrafish. Dev Biol. 2016;409:114-128 pubmed publisher
    ..However Vegf promotes sprouting of the predominantly venous plexus and Bmp promotes outgrowth of the structure. We propose that the SIVP is a unique model to understand novel mechanisms utilized in organ-specific angiogenesis. ..
  60. Hermans K, Claes F, Vandevelde W, Zheng W, Geudens I, Orsenigo F, et al. Role of synectin in lymphatic development in zebrafish and frogs. Blood. 2010;116:3356-66 pubmed publisher
    ..Synectin genetically interacted with Vegfr3 and neuropilin-2a in regulating lymphangiogenesis...
  61. Dunworth W, Cardona Costa J, Bozkulak E, Kim J, Meadows S, Fischer J, et al. Bone morphogenetic protein 2 signaling negatively modulates lymphatic development in vertebrate embryos. Circ Res. 2014;114:56-66 pubmed publisher
    ..Our data identify BMP2 as a key negative regulator for the emergence of the lymphatic lineage during vertebrate development. ..
  62. Zaucker A, Mercurio S, Sternheim N, Talbot W, Marlow F. notch3 is essential for oligodendrocyte development and vascular integrity in zebrafish. Dis Model Mech. 2013;6:1246-59 pubmed publisher
    ..Our analysis of zebrafish notch3 mutants indicates that Notch3 regulates OPC development and mbp gene expression in larvae, and maintains vascular integrity in adults...
  63. Pan W, Pham V, Stratman A, Castranova D, Kamei M, Kidd K, et al. CDP-diacylglycerol synthetase-controlled phosphoinositide availability limits VEGFA signaling and vascular morphogenesis. Blood. 2012;120:489-98 pubmed publisher
    ..These results suggest that availability of CDS-controlled resynthesis of phosphoinositides is essential for angiogenesis. ..
  64. Watson O, Novodvorsky P, Gray C, Rothman A, Lawrie A, Crossman D, et al. Blood flow suppresses vascular Notch signalling via dll4 and is required for angiogenesis in response to hypoxic signalling. Cardiovasc Res. 2013;100:252-61 pubmed publisher
    ..These data indicate important differences in hypoxia-driven vs. developmental angiogenesis. ..
  65. Chen J, Zhu R, Li F, Liang Y, Wang C, Qin Y, et al. MicroRNA-126a Directs Lymphangiogenesis Through Interacting With Chemokine and Flt4 Signaling in Zebrafish. Arterioscler Thromb Vasc Biol. 2016;36:2381-2393 pubmed
    ..revealed that Cxcl12a signaling acted downstream of miR-126a during parachordal lymphangioblast extension, whereby Flt4 signaling acts as a cooperator of miR-126a, allowing it to modulate lymphangiogenic sprout formation...
  66. Herbert S, Cheung J, Stainier D. Determination of endothelial stalk versus tip cell potential during angiogenesis by H2.0-like homeobox-1. Curr Biol. 2012;22:1789-94 pubmed publisher
    ..Hence, Hlx1-mediated maintenance of SC potential regulates angiogenesis, a finding that may have novel implications for sprouting morphogenesis of other tissues. ..
  67. Hogan B, Bussmann J, Wolburg H, Schulte Merker S. ccm1 cell autonomously regulates endothelial cellular morphogenesis and vascular tubulogenesis in zebrafish. Hum Mol Genet. 2008;17:2424-32 pubmed publisher
    ..Finally, we show that ccm1 function is cell autonomous, suggesting that it is endothelial cellular morphogenesis that is regulated by CCM proteins during development and pathogenesis. ..
  68. Delvaeye M, De Vriese A, Zwerts F, Betz I, Moons M, Autiero M, et al. Role of the 2 zebrafish survivin genes in vasculo-angiogenesis, neurogenesis, cardiogenesis and hematopoiesis. BMC Dev Biol. 2009;9:25 pubmed publisher
  69. Wu T, Wang Y, Song Y, Chen Z, Chen Y, Chiu C, et al. Fine-tune regulation of carboxypeptidase N1 controls vascular patterning during zebrafish development. Sci Rep. 2017;7:1852 pubmed publisher
    ..Consistent with vascular growth defects, loss of cpn1 affects the expression of the vascular markers flt4, mrc1, flk, stabilin, and ephrinb2...
  70. Garnaas M, Moodie K, Liu M, Samant G, Li K, Marx R, et al. Syx, a RhoA guanine exchange factor, is essential for angiogenesis in Vivo. Circ Res. 2008;103:710-6 pubmed publisher
    ..These results identify Syx as an essential contributor to angiogenesis in vivo. ..
  71. Zhao Y, Lin S. Essential role of SH3-domain GRB2-like 3 for vascular lumen maintenance in zebrafish. Arterioscler Thromb Vasc Biol. 2013;33:1280-6 pubmed publisher
  72. Ren X, Gomez G, Zhang B, Lin S. Scl isoforms act downstream of etsrp to specify angioblasts and definitive hematopoietic stem cells. Blood. 2010;115:5338-46 pubmed publisher
  73. Minehata K, Kawahara A, Suzuki T. meis1 regulates the development of endothelial cells in zebrafish. Biochem Biophys Res Commun. 2008;374:647-52 pubmed publisher
    ..Thus, these results implicate that meis1 is a novel regulator involved in endothelial cell development, presumably affecting the vegf signaling pathway. ..
  74. Kwon H, Wang S, Helker C, Rasouli S, Maischein H, Offermanns S, et al. In vivo modulation of endothelial polarization by Apelin receptor signalling. Nat Commun. 2016;7:11805 pubmed publisher
    ..Our study provides new tools to analyse the mechanisms of EC polarization in vivo and reveals an important role in this process for a signalling pathway implicated in cardiovascular disease. ..
  75. He B, Shi X, Man C, Ma A, Ekker S, Chow H, et al. Functions of flt3 in zebrafish hematopoiesis and its relevance to human acute myeloid leukemia. Blood. 2014;123:2518-29 pubmed publisher
    ..This study provides novel insight into the role of flt3 during hematopoiesis and establishes a zebrafish model of FLT3-ITD(+) and FLT3-TKD(+) AML that may facilitate high-throughput screening of novel and personalized agents. ..
  76. Chang H, Wang W, Chiu C, Chen C, Wang Y, Chen Z, et al. Ftr82 Is Critical for Vascular Patterning during Zebrafish Development. Int J Mol Sci. 2017;18: pubmed publisher
    ..Together, we identify teleost-specific ftr82 as a vascular gene that plays an important role for vascular development in zebrafish. ..
  77. Lin M, Price E, Boatman S, Hagedorn E, Trompouki E, Satishchandran S, et al. Angiopoietin-like proteins stimulate HSPC development through interaction with notch receptor signaling. elife. 2015;4: pubmed publisher
    ..Together our data provide insight to the angptl-mediated notch activation through receptor interaction and subsequent activation of myc targets. ..