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VEGF in Development pp 14–29Cite as

VEGF Receptor Signalling in Vertebrate Development

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Part of the book series: Molecular Biology Intelligence Unit ((MBIU))

Abstract

The secreted glycoprotein vascular endothelial growth factor A (VEGF or VEGFA) affects many different cell types and modifies a wide spectrum of cellular behaviours in tissue culture models, including proliferation, migration, differentiation and survival. The versatility of VEGF signalling is reflected in the complex composition of its cell surface receptors and their ability to activate a variety of different downstream signalling molecules. A major challenge for VEGF research is to determine which of the specific signalling pathways identified in vitro control development and homeostasis of tissues containing VEGF-responsive cell types in vivo.

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References

  1. Ruhrberg C. Growing and shaping the vascular tree: Multiple roles for VEGF. Bioessays 2003;25(11):1052–1060.

    Article  PubMed  CAS  Google Scholar 

  2. Praloran V. Structure, biosynthesis and biological roles of monocyte-macrophage colony stimulating factor (CSF-1 or M-CSF). Nouv Rev Fr Hematol 1991;33(4):323–333.

    PubMed  CAS  Google Scholar 

  3. Guerrin M, Moukadiri H, Chollet P et al. Vasculotropin/vascular endothelial growth factor is an autocrine growth factor for human retinal pigment epithelial cells cultured in vitro. J Cell Physiol 1995;164(2):385–394.

    Article  PubMed  CAS  Google Scholar 

  4. Sondell M, Lundborg G, Kanje M. Vascular endothelial growth factor has neurotrophic activity and stimulates axonal outgrowth, enhancing cell survival and Schwann cell proliferation in the peripheral nervous system. J Neurosci 1999;19(14):5731–5740.

    PubMed  CAS  Google Scholar 

  5. Grosskreutz CL, Anand-Apte B, Duplaa C et al. Vascular endothelial growth factor-induced migration of vascular smooth muscle cells in vitro. Microvasc Res 1999;58(2):128–136.

    Article  PubMed  CAS  Google Scholar 

  6. Wang H, Keiser JA. Vascular endothelial growth factor upregulates the expression of matrix metalloproteinases in vascular smooth muscle cells: Role of flt-1. Circ Res 1998;83(8):832–840.

    PubMed  CAS  Google Scholar 

  7. Clauss M, Gerlach M, Gerlach H et al. Vascular permeability factor: A tumor-derived polypeptide that induces endothelial cell and monocyte procoagulant activity, and promotes monocyte migration. J Exp Med 1990;172(6):1535–1545.

    Article  PubMed  CAS  Google Scholar 

  8. Senger DR, Ledbetter SR, Claffey KP et al. Stimulation of endothelial cell migration by vascular permeability factor/vascular endothelial growth factor through cooperative mechanisms involving the alphavbeta3 integrin, osteopontin, and thrombin. Am J Pathol 1996;149(1):293–305.

    PubMed  CAS  Google Scholar 

  9. Cleaver O, Krieg PA. VEGF mediates angioblast migration during development of the dorsal aorta in Xenopus. Development 1998;125(19):3905–3914.

    PubMed  CAS  Google Scholar 

  10. Shalaby F, Ho J, Stanford WL et al. A requirement for Flk1 in primitive and definitive hematopoiesis and vasculogenesis. Cell 1997;89(6):981–990.

    Article  PubMed  CAS  Google Scholar 

  11. Schwarz Q, Gu C, Fujisawa H et al. Vascular endothelial growth factor controls neuronal migration and cooperates with Sema3A to pattern distinct compartments of the facial nerve. Genes Dev 2004;18(22):2822–2834.

    Article  PubMed  CAS  Google Scholar 

  12. Silverman WF, Krum JM, Mani N et al. Vascular, glial and neuronal effects of vascular endothelial growth factor in mesencephalic explant cultures. Neuroscience 1999;90(4):1529–1541.

    Article  PubMed  CAS  Google Scholar 

  13. Zelzer E, Mamluk R, Ferrara N et al. VEGFA is necessary for chondrocyte survival during bone development. Development 2004;131(9):2161–2171.

    Article  PubMed  CAS  Google Scholar 

  14. Maes C, Stockmans I, Moermans K et al. Soluble VEGF isoforms are essential for establishing epiphyseal vascularization and regulating chondrocyte development and survival. J Clin Invest 2004;113(2):188–199.

    PubMed  CAS  Google Scholar 

  15. Olsson AK, Dimberg A, Kreuger J et al. VEGF receptor signalling—In control of vascular function. Nat Rev Mol Cell Biol 2006;7(5):359–371.

    Article  PubMed  CAS  Google Scholar 

  16. Davis-Smyth T, Presta LG, Ferrara N. Mapping the charged residues in the second immunoglobulin-like domain of the vascular endothelial growth factor/placenta growth factor receptor Flt-1 required for binding and structural stability. J Biol Chem 1998;273(6):3216–3222.

    Article  PubMed  CAS  Google Scholar 

  17. Fuh G, Li B, Crowley C et al. Requirements for binding and signaling of the kinase domain receptor for vascular endothelial growth factor. J Biol Chem 1998;273(18):11197–11204.

    Article  PubMed  CAS  Google Scholar 

  18. Shinkai A, Ito M, Anazawa H et al. Mapping of the sites involved in ligand association and dissociation at the extracellular domain of the kinase insert domain-containing receptor for vascular endothelial growth factor. J Biol Chem 1998;273(47):31283–31288.

    Article  PubMed  CAS  Google Scholar 

  19. Cebe-Suarez S, Zehnder-Fjallman A, Ballmer-Hofer K. The role of VEGF receptors in angiogenesis; complex partnerships. Cell Mol Life Sci 2006;63(5):601–615.

    Article  PubMed  CAS  Google Scholar 

  20. Kendall RL, Wang G, DiSalvo J et al. Specificity of vascular endothelial cell growth factor receptor ligand binding domains. Biochem Biophys Res Commun 1994;201(1):326–330.

    Article  PubMed  CAS  Google Scholar 

  21. Huang K, Andersson C, Roomans GM et al. Signaling properties of VEGF receptor-1 and-2 homo-and heterodimers. Int J Biochem Cell Biol 2001;33(4):315–324.

    Article  PubMed  CAS  Google Scholar 

  22. Peters KG, De Vries C, Williams LT. Vascular endothelial growth factor receptor expression during embryogenesis and tissue repair suggests a role in endothelial differentiation and blood vessel growth. Proc Natl Acad Sci USA 1993;90(19):8915–8919.

    Article  PubMed  CAS  Google Scholar 

  23. Gerber HP, Condorelli F, Park J et al. Differential transcriptional regulation of the two vascular endothelial growth factor receptor genes. Flt-1, but not Flk-1/KDR, is up-regulated by hypoxia. J Biol Chem 1997;272(38):23659–23667.

    Article  PubMed  CAS  Google Scholar 

  24. Bellik L, Vinci MC, Filippi S et al. Intracellular pathways triggered by the selective FLT-1-agonist placental growth factor in vascular smooth muscle cells exposed to hypoxia. Br J Pharmacol 2005;146(4):568–575.

    Article  PubMed  CAS  Google Scholar 

  25. Hattori K, Heissig B, Wu Y et al. Placental growth factor reconstitutes hematopoiesis by recruiting VEGFR1(+) stem cells from bone-marrow microenvironment. Nat Med 2002;8(8):841–849.

    PubMed  CAS  Google Scholar 

  26. Bellamy WT. Vascular endothelial growth factor as a target opportunity in hematological malignancies. Curr Opin Oncol 2002;14(6):649–656.

    Article  PubMed  CAS  Google Scholar 

  27. Ishida A, Murray J, Saito Y et al. Expression of vascular endothelial growth factor receptors in smooth muscle cells. J Cell Physiol 2001;188(3):359–368.

    Article  PubMed  CAS  Google Scholar 

  28. Shalaby F, Rossant J, Yamaguchi TP et al. Failure of blood-island formation and vasculogenesis in Flk-1-deficient mice. Nature 1995;376(6535):62–66.

    Article  PubMed  CAS  Google Scholar 

  29. Ogunshola OO, Antic A, Donoghue MJ et al. Paracrine and autocrine functions of neuronal vascular endothelial growth factor (VEGF) in the central nervous system. J Biol Chem 2002;277(13):11410–11415.

    Article  PubMed  CAS  Google Scholar 

  30. Yang X, Cepko CL. Flk-1, a receptor for vascular endothelial growth factor (VEGF), is expressed by retinal progenitor cells. J Neurosci 1996;16(19):6089–6099.

    PubMed  CAS  Google Scholar 

  31. Casella I, Feccia T, Chelucci C et al. Autocrine-paracrine VEGF loops potentiate the maturation of megakaryocytic precursors through Flt1 receptor. Blood 2003;101(4):1316–1323.

    Article  PubMed  CAS  Google Scholar 

  32. Selheim F, Holmsen H, Vassbotn FS. Identification of functional VEGF receptors on human platelets. FEBS Lett 2002;512(1–3):107–110.

    Article  PubMed  CAS  Google Scholar 

  33. Sawano A, Iwai S, Sakurai Y et al. Flt-1, vascular endothelial growth factor receptor 1, is a novel cell surface marker for the lineage of monocyte-macrophages in humans. Blood 2001;97(3):785–791.

    Article  PubMed  CAS  Google Scholar 

  34. Clauss M, Weich H, Breier G et al. The vascular endothelial growth factor receptor Flt-1 mediates biological activities. Implications for a functional role of placenta growth factor in monocyte activation and chemotaxis. J Biol Chem 1996;271(30):17629–17634.

    Article  PubMed  CAS  Google Scholar 

  35. Barleon B, Sozzani S, Zhou D et al. Migration of human monocytes in response to vascular endothelial growth factor (VEGF) is mediated via the VEGF receptor flt-1. Blood 1996;87(8):3336–3343.

    PubMed  CAS  Google Scholar 

  36. Dikov MM, Ohm JE, Ray N et al. Differential roles of vascular endothelial growth factor receptors 1 and 2 in dendritic cell differentiation. J Immunol 2005;174(1):215–222.

    PubMed  CAS  Google Scholar 

  37. Nomura M, Yamagishi S, Harada S et al. Possible participation of autocrine and paracrine vascular endothelial growth factors in hypoxia-induced proliferation of endothelial cells and pericytes. J Biol Chem 1995;270(47):28316–28324.

    Article  PubMed  CAS  Google Scholar 

  38. Kaipainen A, Korhonen J, Pajusola K et al. The related FLT4, FLT1, and KDR receptor tyrosine kinases show distinct expression patterns in human fetal endothelial cells. J Exp Med 1993;178(6):2077–2088.

    Article  PubMed  CAS  Google Scholar 

  39. Fong GH, Rossant J, Gertsenstein M et al. Role of the Flt-1 receptor tyrosine kinase in regulating the assembly of vascular endothelium. Nature 1995;376(6535):66–70.

    Article  PubMed  CAS  Google Scholar 

  40. Fong GH, Zhang L, Bryce DM et al. Increased hemangioblast commitment, not vascular disorganization, is the primary defect in flt-1 knock-out mice. Development 1999;126(13):3015–3025.

    PubMed  CAS  Google Scholar 

  41. Waltenberger J, Claesson-Welsh L, Siegbahn A et al. Different signal transduction properties of KDR and Flt1, two receptors for vascular endothelial growth factor. J Biol Chem 1994;269(43):26988–26995.

    PubMed  CAS  Google Scholar 

  42. Olofsson B, Korpelainen E, Pepper MS et al. Vascular endothelial growth factor B (VEGF-B) binds to VEGF receptor-1 and regulates plasminogen activator activity in endothelial cells. Proc Natl Acad Sci USA 1998;95(20):11709–11714.

    Article  PubMed  CAS  Google Scholar 

  43. Gille H, Kowalski J, Li B et al. Analysis of biological effects and signaling properties of Flt-1 (VEGFR-1) and KDR (VEGFR-2): A reassessment using novel receptor-specific vascular endothelial growth factor mutants. J Biol Chem 2001;276(5):3222–3230.

    Article  PubMed  CAS  Google Scholar 

  44. Hiratsuka S, Minowa O, Kuno J et al. Flt-1 lacking the tyrosine kinase domain is sufficient for normal development and angiogenesis in mice. Proc Natl Acad Sci USA 1998;95(16):9349–9354.

    Article  PubMed  CAS  Google Scholar 

  45. Hiratsuka S, Nakao K, Nakamura K et al. Membrane fixation of vascular endothelial growth factor receptor 1 ligand-binding domain is important for vasculogenesis and angiogenesis in mice. Mol Cell Biol 2005;25(1):346–354.

    Article  PubMed  CAS  Google Scholar 

  46. Kearney JB, Kappas NC, Ellerstrom C et al. The VEGF receptor flt-1 (VEGFR-1) is a positive modulator of vascular sprout formation and branching morphogenesis. Blood 2004;103(12):4527–4535.

    Article  PubMed  CAS  Google Scholar 

  47. Hiratsuka S, Maru Y, Okada A et al. Involvement of Flt-1 tyrosine kinase (vascular endothelial growth factor receptor-1) in pathological angiogenesis. Cancer Res 2001;61(3):1207–1213.

    PubMed  CAS  Google Scholar 

  48. Autiero M, Waltenberger J, Communi D et al. Role of PlGF in the intra-and intermolecular cross talk between the VEGF receptors Flt1 and Flk1. Nat Med 2003;9(7):936–943.

    Article  PubMed  CAS  Google Scholar 

  49. Selvaraj SK, Giri RK, Perelman N et al. Mechanism of monocyte activation and expression of proinflammatory cytochemokines by placenta growth factor. Blood 2003;102(4):1515–1524.

    Article  PubMed  CAS  Google Scholar 

  50. Adini A, Kornaga T, Firoozbakht F et al. Placental growth factor is a survival factor for tumor endothelial cells and macrophages. Cancer Res 2002;62(10):2749–2752.

    PubMed  CAS  Google Scholar 

  51. Park JE, Chen HH, Winer J et al. Placenta growth factor. Potentiation of vascular endothelial growth factor bioactivity, in vitro and in vivo, and high affinity binding to Flt-1 but not to Flk-1/KDR. J Biol Chem 1994;269(41):25646–25654.

    PubMed  CAS  Google Scholar 

  52. Parenti A, Brogelli L, Filippi S et al. Effect of hypoxia and endothelial loss on vascular smooth muscle cell responsiveness to VEGF-A: Role of flt-l/VEGF-receptor-1. Cardiovasc Res 2002;55(1):201–212.

    Article  PubMed  CAS  Google Scholar 

  53. Luttun A, Tjwa M, Moons L et al. Revascularization of ischemic tissues by PlGF treatment, and inhibition of tumor angiogenesis, arthritis and atherosclerosis by anti-Flt1. Nat Med 2002;8(8):831–840.

    PubMed  CAS  Google Scholar 

  54. Grunewald M, Avraham I, Dor Y et al. VEGF-induced adult neovascularization: Recruitment, retention, and role of accessory cells. Cell 2006;124(1):175–189.

    Article  PubMed  CAS  Google Scholar 

  55. Lyden D, Hattori K, Dias S et al. Impaired recruitment of bone-marrow-derived endothelial and hematopoietic precursor cells blocks tumor angiogenesis and growth. Nat Med 2001;7(11):1194–1201.

    Article  PubMed  CAS  Google Scholar 

  56. Matsumoto T, Claesson-Welsh L. VEGF receptor signal transduction. Sci STKE 2001;2001(112):RE21.

    Article  PubMed  CAS  Google Scholar 

  57. Gille H, Kowalski J, Yu L et al. A repressor sequence in the juxtamembrane domain of Flt-1 (VEGFR-1) constitutively inhibits vascular endothelial growth factor-dependent phosphatidylinositol 3′-kinase activation and endothelial cell migration. EMBO J 2000;19(15):4064–4073.

    Article  PubMed  CAS  Google Scholar 

  58. Chou MT, Wang J, Fujita DJ. Src kinase becomes preferentially associated with the VEGFR, KDR/Flk-1, following VEGF stimulation of vascular endothelial cells. BMC Biochem 2002;3:32.

    Article  PubMed  Google Scholar 

  59. Stein PL, Vogel H, Soriano P. Combined deficiencies of Src, Fyn, and Yes tyrosine kinases in mutant mice. Genes Dev 1994;8(17):1999–2007.

    Article  PubMed  CAS  Google Scholar 

  60. Ito N, Huang K, Claesson-Welsh L. Signal transduction by VEGF receptor-1 wild type and mutant proteins. Cell Signal 2001;13(11):849–854.

    Article  PubMed  CAS  Google Scholar 

  61. Terman BI, Dougher-Vermazen M, Carrion ME et al. Identification of the KDR tyrosine kinase as a receptor for vascular endothelial cell growth factor. Biochem Biophys Res Commun 1992;187(3):1579–1586.

    Article  PubMed  CAS  Google Scholar 

  62. Quinn TP, Peters KG, De Vries C et al. Fetal liver kinase 1 is a receptor for vascular endothelial growth factor and is selectively expressed in vascular endothelium. Proc Natl Acad Sci USA 1993;90(16):7533–7537.

    Article  PubMed  CAS  Google Scholar 

  63. Bernatchez PN, Soker S, Sirois MG. Vascular endothelial growth factor effect on endothelial cell proliferation, migration, and platelet-activating factor synthesis is Flk-1-dependent. J Biol Chem 1999;274(43):31047–31054.

    Article  PubMed  CAS  Google Scholar 

  64. Takahashi T, Yamaguchi S, Chida K et al. A single autophosphorylation site on KDR/Flk-1 is essential for VEGF-A-dependent activation of PLC-gamma and DNA synthesis in vascular endothelial cells. Embo J 2001;20(11):2768–2778.

    Article  PubMed  CAS  Google Scholar 

  65. Werdich XQ, Penn JS. Src, Fyn and Yes play differential roles in VEGF-mediated endothelial cell events. Angiogenesis 2005; 8(4):315–326.

    Article  PubMed  CAS  Google Scholar 

  66. Eliceiri BP, Paul R, Schwartzberg PL et al. Selective requirement for Src kinases during VEGF-induced angiogenesis and vascular permeability. Mol Cell 1999; 4(6):915–924.

    Article  PubMed  CAS  Google Scholar 

  67. Rajagopal K, Sommers CL, Decker DC et al. RIBP, a novel Rlk/Txk-and itk-binding adaptor protein that regulates T cell activation. J Exp Med 1999; 190(11):1657–1668.

    Article  PubMed  CAS  Google Scholar 

  68. Lamalice L, Houle F, Jourdan G et al. Phosphorylation of tyrosine 1214 on VEGFR2 is required for VEGF-induced activation of Cdc42 upstream of SAPK2/p38. Oncogene 2004; 23(2):434–445.

    Article  PubMed  CAS  Google Scholar 

  69. Holmqvist K, Cross MJ, Rolny C et al. The adaptor protein shb binds to tyrosine 1175 in vascular endothelial growth factor (VEGF) receptor-2 and regulates VEGF-dependent cellular migration. J Biol Chem 2004; 279(21):22267–22275.

    Article  PubMed  CAS  Google Scholar 

  70. Sakurai Y, Ohgimoto K, Kataoka Y et al. Essential role of Flk-1 (VEGF receptor 2) tyrosine residue 1173 in vasculogenesis in mice. Proc Natl Acad Sci USA 2005; 102(4):1076–1081.

    Article  PubMed  CAS  Google Scholar 

  71. Aouadi M, Binetruy B, Caron L et al. Role of MAPKs in development and differentiation: Lessons from knockout mice. Biochimie 2006; 88(9):1091–1098.

    Article  PubMed  CAS  Google Scholar 

  72. Lai KM, Pawson T. The ShcA phosphotyrosine docking protein sensitizes cardiovascular signaling in the mouse embryo. Genes Dev 2000; 14(9):1132–1145.

    PubMed  CAS  Google Scholar 

  73. Sakai R, Henderson JT, O’Bryan JP et al. The mammalian ShcB and ShcC phosphotyrosine docking proteins function in the maturation of sensory and sympathetic neurons. Neuron 2000; 28(3):819–833.

    Article  PubMed  CAS  Google Scholar 

  74. Kriz V, Agren N, Lindholm CK et al. The SHB adapter protein is required for normal maturation of mesoderm during in vitro differentiation of embryonic stem cells. J Biol Chem 2006; 281(45):34484–34491.

    Article  PubMed  CAS  Google Scholar 

  75. Haigh JJ, Morelli PI, Gerhardt H et al. Cortical and retinal defects caused by dosage-dependent reductions in VEGF-A paracrine signaling. Dev Biol 2003; 262(2):225–24l.

    Article  PubMed  CAS  Google Scholar 

  76. Lee S, Chen TT, Barber CL et al. Autocrine VEGF signaling is required for vascular homeostasis. Cell 2007; 130(4):691–703.

    Article  PubMed  CAS  Google Scholar 

  77. Serini G, Valdembri D, Bussolino F. Integrins and angiogenesis: A sticky business. Exp Cell Res 2006; 312(5):651–658.

    Article  PubMed  CAS  Google Scholar 

  78. Carmeliet P, Collen D. Molecular basis of angiogenesis: Role of VEGF and VE-cadherin. Ann NY Acad Sci 2000; 902:249–262, (discussion 262–244).

    Article  PubMed  CAS  Google Scholar 

  79. Carmeliet P, Lampugnani MG, Moons L et al. Targeted deficiency or cytosolic truncation of the VE-cadherin gene in mice impairs VEGF-mediated endothelial survival and angiogenesis. Cell 1999; 98(2):147–157.

    Article  PubMed  CAS  Google Scholar 

  80. Sun JF, Phung T, Shiojima I et al. Microvascular patterning is controlled by fine-tuning the Akt signal. Proc Natl Acad Sci USA 2005; 102(1):128–133.

    Article  PubMed  CAS  Google Scholar 

  81. Gerber HP, McMurtrey A, Kowalski J et al. Vascular endothelial growth factor regulates endothelial cell survival through the phosphatidylinositol 3′-kinase/Akt signal transduction pathway. Requirement for Flk-1/KDR activation. J Biol Chem 1998; 273(46):30336–30343.

    Article  PubMed  CAS  Google Scholar 

  82. Thakker GD, Hajjar DP, Muller WA et al. The role of phosphatidylinositol 3-kinase in vascular endothelial growth factor signaling. J Biol Chem 1999; 274(15):10002–10007.

    Article  PubMed  CAS  Google Scholar 

  83. Lampugnani MG, Orsenigo F, Gagliani MC et al. Vascular endothelial cadherin controls VEGFR-2 internalization and signaling from intracellular compartments. J Cell Biol 2006; 174(4):593–604.

    Article  PubMed  CAS  Google Scholar 

  84. Guo DQ, Wu LW, Dunbar JD et al. Tumor necrosis factor employs a protein-tyrosine phosphatase to inhibit activation of KDR and vascular endothelial cell growth factor-induced endothelial cell proliferation. J Biol Chem 2000; 275(15):11216–11221.

    Article  PubMed  CAS  Google Scholar 

  85. Gallicchio M, Mitola S, Valdembri D et al. Inhibition of vascular endothelial growth factor receptor 2-mediated endothelial cell activation by Axl tyrosine kinase receptor. Blood 2005; 105(5):1970–1976.

    Article  PubMed  CAS  Google Scholar 

  86. Huang L, Sankar S, Lin C et al. HCPTPA, a protein tyrosine phosphatase that regulates vascular endothelial growth factor receptor-mediated signal transduction and biological activity. J Biol Chem 1999; 274(53):38183–38188.

    Article  PubMed  CAS  Google Scholar 

  87. Gitay-Goren H, Cohen T, Tessler S et al. Selective binding of VEGF121 to one of the three vascular endothelial growth factor receptors of vascular endothelial cells. J Biol Chem 1996; 271(10):5519–5523.

    Article  PubMed  CAS  Google Scholar 

  88. Soker S, Fidder H, Neufeld G et al. Characterization of novel vascular endothelial growth factor (VEGF) receptors on tumor cells that bind VEGF165 via its exon 7-encoded domain. J Biol Chem 1996; 271(10):5761–5767.

    Article  PubMed  CAS  Google Scholar 

  89. Takagi S, Tsuji T, Amagai T et al. Specific cell surface labels in the visual centers of Xenopus laevis tadpole identified using monoclonal antibodies. Dev Biol 1987; 122(1):90–100.

    Article  PubMed  CAS  Google Scholar 

  90. Fujisawa H, Ohtsuki T, Takagi S et al. An aberrant retinal pathway and visual centers in Xenopus tadpoles share a common cell surface molecule, A5 antigen. Dev Biol 1989; 135(2):231–240.

    Article  PubMed  CAS  Google Scholar 

  91. He Z, Tessier-Lavigne M. Neuropilin is a receptor for the axonal chemorepellent Semaphorin III. Cell 1997; 90(4):739–751.

    Article  PubMed  CAS  Google Scholar 

  92. Kolodkin AL, Levengood DV, Rowe EG et al. Neuropilin is a semaphorin III receptor. Cell 1997; 90(4):753–762.

    Article  PubMed  CAS  Google Scholar 

  93. Chen H, Chedotal A, He Z et al. Neuropilin-2, a novel member of the neuropilin family, is a high affinity receptor for the semaphorins Sema E and Sema IV but not Sema III. Neuron 1997; 19(3):547–559.

    Article  PubMed  CAS  Google Scholar 

  94. Gluzman-Poltorak Z, Cohen T, Herzog Y et al. Neuropilin-2 is a receptor for the vascular endothelial growth factor (VEGF) forms VEGF-145 and VEGF-165 [corrected]. J Biol Chem 2000; 275(24):18040–18045.

    Article  PubMed  CAS  Google Scholar 

  95. Takagi S, Hirata T, Agata K et al. The A5 antigen, a candidate for the neuronal recognition molecule, has homologies to complement components and coagulation factors. Neuron 1991; 7(2):295–307.

    Article  PubMed  CAS  Google Scholar 

  96. Lee CC, Kreusch A, McMullan D et al. Crystal structure of the human neuropilin-1 b1 domain. Structure 2003; 11(1):99–108.

    Article  PubMed  CAS  Google Scholar 

  97. Nakamura F, Tanaka M, Takahashi T et al. Neuropilin-1 extracellular domains mediate semaphorin D/III-induced growth cone collapse. Neuron 1998; 21(5):1093–1100.

    Article  PubMed  CAS  Google Scholar 

  98. Rohm B, Ottemeyer A, Lohrum M et al. Plexin/neuropilin complexes mediate repulsion by the axonal guidance signal semaphorin 3A. Mech Dev 2000; 93(1–2):95–104.

    Article  PubMed  CAS  Google Scholar 

  99. Tamagnone L, Artigiani S, Chen H et al. Plexins are a large family of receptors for transmembrane, secreted, and GPI-anchored semaphorins in vertebrates. Cell 1999; 99(1):71–80.

    Article  PubMed  CAS  Google Scholar 

  100. Soker S, Takashima S, Miao HQ et al. Neuropilin-1 is expressed by endothelial and tumor cells as an isoform-specific receptor for vascular endothelial growth factor. Cell 1998; 92(6):735–745.

    Article  PubMed  CAS  Google Scholar 

  101. Kitsukawa T, Shimizu M, Sanbo M et al. Neuropilin-semaphorin III/D-mediated chemorepulsive signals play a crucial role in peripheral nerve projection in mice. Neuron 1997; 19(5):995–1005.

    Article  PubMed  CAS  Google Scholar 

  102. Kawasaki T, Bekku Y, Suto F et al. Requirement of neuropilin 1-mediated Sema3A signals in patterning of the sympathetic nervous system. Development 2002; 129(3):671–680.

    PubMed  CAS  Google Scholar 

  103. Marin O, Yaron A, Bagri A et al. Sorting of striatal and cortical interneurons regulated by semaphorin-neuropilin interactions. Science 2001; 293(5531):872–875.

    Article  PubMed  CAS  Google Scholar 

  104. Giger RJ, Cloutier JF, Sahay A et al. Neuropilin-2 is required in vivo for selective axon guidance responses to secreted semaphorins. Neuron 2000; 25(1):29–41.

    Article  PubMed  CAS  Google Scholar 

  105. Chen H, Bagri A, Zupicich JA et al. Neuropilin-2 regulates the development of selective cranial and sensory nerves and hippocampal mossy fiber projections. Neuron 2000; 25(1):43–56.

    Article  PubMed  Google Scholar 

  106. Herzog Y, Kalcheim C, Kahane N et al. Differential expression of neuropilin-1 and neuropilin-2 in arteries and veins. Mech Dev 2001; 109(1):115–119.

    Article  PubMed  CAS  Google Scholar 

  107. Kitsukawa T, Shimono A, Kawakami A et al. Overexpression of a membrane protein, neuropilin, in chimeric mice causes anomalies in the cardiovascular system, nervous system and limbs. Development 1995; 121(12):4309–4318.

    PubMed  CAS  Google Scholar 

  108. Kawasaki T, Kitsukawa T, Bekku Y et al. A requirement for neuropilin-1 in embryonic vessel formation. Development 1999; 126(21):4895–4902.

    PubMed  CAS  Google Scholar 

  109. Lee P, Goishi K, Davidson AJ et al. Neuropilin-1 is required for vascular development and is a mediator of VEGF-dependent angiogenesis in zebrafish. Proc Natl Acad Sci USA 2002; 99(16):10470–10475.

    Article  PubMed  CAS  Google Scholar 

  110. Wang L, Mukhopadhyay D, Xu X. C terminus of RGS-GAIP-interacting protein conveys neuropilin-1-mediated signaling during angiogenesis. FASEB J 2006; 20(9):1513–1515.

    Article  PubMed  CAS  Google Scholar 

  111. Yuan L, Moyon D, Pardanaud L et al. Abnormal lymphatic vessel development in neuropilin 2 mutant mice. Development 2002; 129(20):4797–4806.

    PubMed  CAS  Google Scholar 

  112. Takashima S, Kitakaze M, Asakura M et al. Targeting of both mouse neuropilin-1 and neuropilin-2 genes severely impairs developmental yolk sac and embryonic angiogenesis. Proc Natl Acad Sci USA 2002; 99(6):3657–3662.

    Article  PubMed  CAS  Google Scholar 

  113. Favier B, Alam A, Barron P et al. Neuropilin-2 interacts with VEGFR-2 and VEGFR-3 and promotes human endothelial cell survival and migration. Blood 2006; 108(4):1243–1250.

    Article  PubMed  CAS  Google Scholar 

  114. Gu C, Rodriguez ER, Reimert DV et al. Neuropilin-1 conveys semaphorin and VEGF signaling during neural and cardiovascular development. Dev Cell 2003; 5(1):45–57.

    Article  PubMed  CAS  Google Scholar 

  115. Ruhrberg C, Gerhardt H, Golding M et al. Spatially restricted patterning cues provided by heparin-binding VEGF-A control blood vessel branching morphogenesis. Genes Dev 2002; 16(20):2684–2698.

    Article  PubMed  CAS  Google Scholar 

  116. Gerhardt H, Ruhrberg C, Abramsson A et al. Neuropilin-1 is required for endothelial tip cell guidance in the developing central nervous system. Dev Dyn 2004; 231(3):503–509.

    Article  PubMed  CAS  Google Scholar 

  117. Miao HQ, Soker S, Feiner L et al. Neuropilin-1 mediates collapsin-1/semaphorin III inhibition of endothelial cell motility: Functional competition of collapsin-1 and vascular endothelial growth factor-165. J Cell Biol 1999; 146(1):233–242.

    Article  PubMed  CAS  Google Scholar 

  118. Vieira JM, Schwarz Q, Ruhrberg C. Selective requirements for NRP1 ligands during neurovascular patterning. Development 2007; 134(10):1833–1843.

    Article  PubMed  CAS  Google Scholar 

  119. Fuh G, Garcia KC, de Vos AM. The interaction of neuropilin-1 with vascular endothelial growth factor and its receptor flt-1. J Biol Chem 2000; 275(35):26690–26695.

    PubMed  CAS  Google Scholar 

  120. Whitaker GB, Limberg BJ, Rosenbaum JS. Vascular endothelial growth factor receptor-2 and neuropilin-1 form a receptor complex that is responsible for the differential signaling potency of VEGF(165) and VEGF(121). J Biol Chem 2001; 276(27):25520–25531.

    Article  PubMed  CAS  Google Scholar 

  121. Soker S, Miao HQ, Nomi M et al. VEGF165 mediates formation of complexes containing VEGFR-2 and neuropilin-1 that enhance VEGF165-receptor binding. J Cell Biochem 2002; 85(2):357–368.

    Article  PubMed  CAS  Google Scholar 

  122. Wang L, Zeng H, Wang P et al. Neuropilin-1-mediated vascular permeability factor/vascular endothelial growth factor-dependent endothelial cell migration. J Biol Chem 2003; 278(49):48848–48860.

    Article  PubMed  CAS  Google Scholar 

  123. Cai H, Reed RR. Cloning and characterization of neuropilin-1-interacting protein: A PSD-95/Dlg/ZO-1 domain-containing protein that interacts with the cytoplasmic domain of neuropilin-1. J Neurosci 1999; 19(15):6519–6527.

    PubMed  CAS  Google Scholar 

  124. Chittenden TW, Claes F, Lanahan AA et al. Selective regulation of arterial branching morphogenesis by synectin. Dev Cell 2006; 10(6):783–795.

    Article  PubMed  CAS  Google Scholar 

  125. Mukouyama YS, Gerber HP, Ferrara N et al. Peripheral nerve-derived VEGF promotes arterial differentiation via neuropilin 1-mediated positive feedback. Development 2005; 132(5):941–952.

    Article  PubMed  CAS  Google Scholar 

  126. Stalmans I, Ng YS, Rohan R et al. Arteriolar and venular patterning in retinas of mice selectively expressing VEGF isoforms. J Clin Invest 2002; 109(3):327–336.

    PubMed  CAS  Google Scholar 

  127. Bernfield M, Kokenyesi R, Kato M et al. Biology of the syndecans: A family of transmembrane heparan sulfate proteoglycans. Annu Rev Cell Biol 1992; 8:365–393.

    Article  PubMed  CAS  Google Scholar 

  128. Park JE, Keller GA, Ferrara N. The vascular endothelial growth factor (VEGF) isoforms: Differential deposition into the subepithelial extracellular matrix and bioactivity of extracellular matrix-bound VEGF. Mol Biol Cell 1993; 4(12):1317–1326.

    PubMed  CAS  Google Scholar 

  129. Gerhardt H, Golding M, Fruttiger M et al. VEGF guides angiogenic sprouting utilizing endothelial tip cell filopodia. J Cell Biol 2003; 161(6):1163–1177.

    Article  PubMed  CAS  Google Scholar 

  130. Tessler S, Rockwell P, Hicklin D et al. Heparin modulates the interaction of VEGF165 with soluble and cell associated flk-1 receptors. J Biol Chem 1994; 269(17):12456–12461.

    PubMed  CAS  Google Scholar 

  131. Terman B, Khandke L, Dougher-Vermazan M et al. VEGF receptor subtypes KDR and FLT1 show different sensitivities to heparin and placenta growth factor. Growth Factors 1994; 11(3):187–195.

    Article  PubMed  CAS  Google Scholar 

  132. Ashikari-Hada S, Habuchi H, Kariya Y et al. Heparin regulates vascular endothelial growth factor 165-dependent mitogenic activity, tube formation, and its receptor phosphorylation of human endothelial cells: Comparison of the effects of heparin and modified heparins. J Biol Chem 2005; 280(36):31508–31515.

    Article  PubMed  CAS  Google Scholar 

  133. Jakobsson L, Kreuger J, Holmborn K et al. Heparan sulfate in trans potentiates VEGFR-mediated angiogenesis. Dev Cell 2006; 10(5):625–634.

    Article  PubMed  CAS  Google Scholar 

  134. Shintani Y, Takashima S, Asano Y et al. Glycosaminoglycan modification of neuropilin-1 modulates VEGFR2 signaling. Embo J 2006; 25(13):3045–3055.

    Article  PubMed  CAS  Google Scholar 

  135. Dougher M, Terman BI. Autophosphorylation of KDR in the kinase domain is required for maximal VEGF-stimulated kinase activity and receptor internalization. Oncogene 1999; 18(8):1619–1627.

    Article  PubMed  CAS  Google Scholar 

  136. Feng Y, Venema VJ, Venema RC et al. VEGF induces nuclear translocation of Flk-1/KDR, endothelial nitric oxide synthase, and caveolin-1 in vascular endothelial cells. Biochem Biophys Res Commun 1999; 256(1):192–197.

    Article  PubMed  CAS  Google Scholar 

  137. Li W, Keller G. VEGF nuclear accumulation correlates with phenotypical changes in endothelial cells. J Cell Sci 2000; 113 (Pt 9):1525–1534.

    PubMed  CAS  Google Scholar 

  138. Ilan N, Tucker A, Madri JA. Vascular endothelial growth factor expression, beta-catenin tyrosine phosphorylation, and endothelial proliferative behavior: A pathway for transformation? Lab Invest 2003; 83(8):1105–1115.

    Article  PubMed  CAS  Google Scholar 

  139. Santos SC, Miguel C, Domingues I et al. VEGF and VEGFR-2 (KDR) internalization is required for endothelial recovery during wound healing. Exp Cell Res 2007; 313(8):1561–1574.

    Article  PubMed  CAS  Google Scholar 

  140. Pan Q, Chanthery Y, Liang WC et al. Blocking neuropilin-1 function has an additive effect with anti-VEGF to inhibit tumor growth. Cancer Cell 2007; 11(1):53–67.

    Article  PubMed  CAS  Google Scholar 

  141. Hamada K, Sasaki T, Koni PA et al. The PTEN/PI3K pathway governs normal vascular development and tumor angiogenesis. Genes Dev 2005; 19(17):2054–2065.

    Article  PubMed  CAS  Google Scholar 

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  1. Institute of Ophthalmology, University College London, 11-43 Bath Street, London, EC1V 9EL, UK

    Joaquim Miguel Vieira & Quenten Schwarz

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  1. Joaquim Miguel Vieira
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  2. Christiana Ruhrberg
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Vieira, J.M., Ruhrberg, C., Schwarz, Q. (2008). VEGF Receptor Signalling in Vertebrate Development. In: VEGF in Development. Molecular Biology Intelligence Unit. Springer, New York, NY. https://doi.org/10.1007/978-0-387-78632-2_2

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