The Role of Vascular Endothelial Growth Factors and Their Receptors During Embryonic Vascular Development

  • Ingo Flamme
  • Georg Breier
Part of the Cardiovascular Molecular Morphogenesis book series (CARDMM)

Abstract

The cardiovascular system of vertebrates emanates from the mesodermal layer of the primitive embryo. Angioblasts giving rise to endothelial cells and hematoblasts giving rise to blood cells differentiate from their fibroblast-like precursors shortly after having migrated through the primitive streak during gastrulation (Gonzalez Crussi, 1971). Nascent angioblasts and their assembly into the primordial vascular plexus were made visible for the first time in the quail embryo by means of monoclonal antibodies, which recognize epitopes on endothelial and hematopoietic cells (MB-1 and QH-1) (Peault et al., 1983;Pardanaud et al., 1987). The first angioblasts originate at the periphery of the extraembryonic mesoderm, but a little later (when the head fold is formed at the one-somite stage) in the embryo proper (Pardanaud et al., 1987;Coffin and Poole, 1988;Coffin and Poole, 1989). Along the anterior intestinal portal they establish the primordia of the endocardium, and along the lateral edges of the somites they establish the primordia of large body vessels, which become interconnected to the extraembryonic vasculature at the two-somite stage. The morphogenesis of the early vasculature has been described in a series of comprehensive articles (His, 1900;Evans, 1909;Sabin, 1917,Sabin, 1920;Gonzalez Crussi, 1971;Haar and Ackerman, 1971;Lanot, 1980;Hirakow and Hiruma, 1981; Pardanaud et al., 1987; Coffin and Poole, 1989;De Ruiter et al., 1991,De Ruiter et al., 1993).

Keywords

Permeability Migration Tyrosine Leukemia Heparin 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Aase, K., Lymboussaki, A., Kaipainen, A., Olofsson, B., Alitalo, K., Eriksson, U. (1999). Localization of VEGF-B in the mouse embryo suggests a paracrine role of the growth factor in the developing vasculature. Dev Dyn 215:12–25.PubMedGoogle Scholar
  2. Achen, M., Gad, J., Stacker, S., Wilks, A. (1997). Placenta growth factor and vascular endothelial growth factor are co-expressed during early embryonic development. Growth Factors 15:69–80.PubMedGoogle Scholar
  3. Achen, M., Jeltsch, M., Kukk, E., et al. (1998). Vascular endothelial growth factor D (VEGFD) is a ligand for the tyrosine kinases VEGF receptor 2 (Flkl) and VEGF receptor 3 (F1í4). Proc Natl Acad Sci USA 95:548–553.PubMedGoogle Scholar
  4. Adair, T.H., Gay, W.J., Montani, J.P. (1990). Growth regulation of the vascular system: evidence for a metabolic hypothesis. Am J Physiol 259:R393–R404.PubMedGoogle Scholar
  5. Adams, R.H., Wilkinson, G.A., Weiss, C., et al. (1999). Roles of ephrinB ligands and EphB receptors in cardiovascular development: demarcation of arterial/venous domains, vascular morphogenesis, and sprouting angiogenesis. Genes Dev 13:295–306.PubMedGoogle Scholar
  6. Aiello, L.P., Pierce, E.A., Foley, E.D., et al. (1995). Suppression of retinal neovascularizationin vivoby inhibition of vascular endothelial growth factor (VEGF) using soluble VEGF-receptor chimeric proteins. Proc Natl Acad Sci USA 92:10457–10461.PubMedGoogle Scholar
  7. Alon, T., Hemo, I., Itin, A., Pe’er, J., Stone, J., Keshet, E. (1995). Vascular endothelial growth factor acts as a survival factor for newly formed retinal vessels and has implications for retinopathy of prematurity. Nature Med 1:1024–1028.PubMedGoogle Scholar
  8. Arany, Z., Huang, L.E., Eckner, R., et al. (1996). An essential role for p300/CBP in the cellular response to hypoxia. Proc Natl Acad Sci USA 93:12969–12973.PubMedGoogle Scholar
  9. Asahara, T., Masuda, H., Takahashi, T., et al. (1999). Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization. Circ Res 85:221–228.PubMedGoogle Scholar
  10. Asahara, T., Murohara, T., Sullivan, A., et al. (1997). Isolation of putative progenitor endothelial cells for angiogenesis. Science 275:964–967.PubMedGoogle Scholar
  11. Azar, Y., Eyal-Giladi, H. (1979). Marginal zone cells-the primitive streak-inducing component of the primary hypoblast in the chick. J Embryol Exp Morphol 52:79–88.PubMedGoogle Scholar
  12. Baird, A. (2000). Fibroblast growth factors and their receptors. In: Rubanyi, G.M., ed.Angiogenesis in health and diseasepp. 75–88. New York: Marcell Dekker.Google Scholar
  13. Barleon, B., Sozzani, S., Zhou, D., Weich, H.A., Mantovani, A., Marme, D. (1996). Migration of human monocytes in response to vascular endothelial growth factor (VEGF) is mediated via the VEGF receptor Flt-1. Blood 87:3336–3343.PubMedGoogle Scholar
  14. Baumhueter, S., Dybdal, N., Kyle, C., Lasky, L. (1994). Global vascular expression of murine CD34, a sialomucine-like endothelial ligand for L-selectin. Blood 84:2554–2565.PubMedGoogle Scholar
  15. Benjamin, L., Hemo, I., Keshet, E. (1998). A plasticity window for blood vessel remodelling is defined by pericyte coverage of the preformed endothelial network and is regulated by PDGF-B and VEGF. Development 125:1591–1598.PubMedGoogle Scholar
  16. Benjamin, L.E., Keshet, E. (1997). Conditional switching of vascular endothelial growth factor (VEGF) expression in tumors: induction of endothelial cell shedding and regression of hemangioblastoma-like vessels by VEGF withdrawal. Proc Natl Acad Sci USA 94:8761–8766.PubMedGoogle Scholar
  17. Bielinska, M., Narita, N., Heikinheimo, M., Porter, S.B., Wilson, D.B. (1996). Erythropoiesis and vasculogenesis in embryoid bodies lacking visceral yolk sac endoderm. Blood 88:3720–3730.PubMedGoogle Scholar
  18. Bogers, A.J.J.C., Gittenberger-de Groot, A.C., Poelmann, R.E., Péault, B.M., Huysmans, H.A. (1989). Development of the origin of the coronary arteries, a matter of ingrowth or outgrowth? Anat Embryol 180:437–441.PubMedGoogle Scholar
  19. Breier, G., Albrecht, U., Sterrer, S., Risau, W. (1992). Expression of vascular endothelial growth factor during embryonic angiogenesis and endothelial cell differentiation. Development 114:521–532.PubMedGoogle Scholar
  20. Breier, G., Clauss, M., Risau, W. (1995). Coordinate expression of vascular endothelial growth factor receptor-1 (Flt-1) and its ligand suggests a paracrine regulation of murine vascular development. Dev Dyn 204:228–239.PubMedGoogle Scholar
  21. Brown, L.F., Berse, B., Tognazzi, K., et al. (1992). Vascular permeability factor mRNA and protein expression in human kidney. Kidney Int 42:1457–1461.PubMedGoogle Scholar
  22. Burgess, W.H., Maciag, T. (1989). The heparin-binding (fibroblast) growth factor family of proteins. Annu Rev Biochem 58:575–606.PubMedGoogle Scholar
  23. Cao, Y., Chen, H., Zhou, L., et al. (1996). Heterodimers of placenta growth factor/vascular endothelial growth factor. Endothelial activity, tumor cell expression, and high affinity binding to Flk-1/KDR. J Biol Chem 271:3154–3162.PubMedGoogle Scholar
  24. Carmeliet, P., Collen, D. (1999). Role of vascular endothelial growth factor and vascular endothelial growth factor receptors in vascular development. Curr Top Microbiol Immunol 237:133–158.PubMedGoogle Scholar
  25. Carmeliet, P., Ferreira, V., Breier, G., et al. (1996). Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele. Nature 380:435–439.PubMedGoogle Scholar
  26. Carmeliet, P., Lampugnani, M.G., Moons, L., et al. (1999a). Targeted deficiency or cytosolic truncation of the VE-cadherin gene in mice impairs VEGF-mediated endothelial survival and angiogenesis. Cell 98:147–157.Google Scholar
  27. Carmeliet, P., Ng, Y.S., Nuyens, D., et al. (1999b). Impaired myocardial angiogenesis and ischemic cardiomyopathy in mice lacking the vascular endothelial growth factor isoforms VEGF164 and VEGF188. Nat Med 5:495–502.Google Scholar
  28. Carroll, S.M., White, F.C., Bloor, C.M. (1994). Hypoxia regulates vascular endothelial growth-factor (VEGF) messenger-RNA levels by a posttranscriptional mechanism. Circulation 90:521.Google Scholar
  29. Chapman, W. (1918). The effect of the heart-beat upon the development of the vascular system in the chick. Am J Anat 23:175–203.Google Scholar
  30. Choi, K., Kennedy, M., Kazarov, A., Papadimitriou, J., Keller, G. (1998). A common precursor for hematopoietic and endothelial cells. Development 125:725–732.PubMedGoogle Scholar
  31. Christ, B., Grim, M., Wilting, J., von Kirschhofer, K., Wachtler, F. (1991). Differentiation of endothelial cells in avian embryos does not depend on gastrulation. Acta Histochem 91:193–199.PubMedGoogle Scholar
  32. Clark, D.E., Smith, S.K., Licence, D., Evans, A.L., Charnock-Jones, D.S. (1998). Comparison of expression patterns for placenta growth factor, vascular endothelial growth factor (VEGF), VEGF-B and VEGF-C in the human placenta throughout gestation. J Endocrinol 159:459–467.PubMedGoogle Scholar
  33. Clauss, M., Gerlach, M., Gerlach, H., et al. (1990). Vascular-permeability factor-a tumor-derived polypeptide that induces endothelial-cell and monocyte procoagulant activity, and promotes monocyte migration. J Exp Med 172:1535–1545.PubMedGoogle Scholar
  34. Clauss, M., Grell, M., Fangmann, C., Fiers, W., Scheurich, P., Risau, W. (1996a). Synergistic induction of endothelial tissue factor by tumor necrosis factor and vascular endothelial growth factor: functional analysis of the tumor necrosis factor receptors. FEBS Lett 390:334–338.Google Scholar
  35. Clauss, M., Weich, H., Breier, G., et al. (1996b). 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 271:17629–17634.Google Scholar
  36. Cleaver, O., Krieg, P. (1998). VEGF mediates angioblast migration during development of the dorsal aorta in Xenopus. Development 125:3905–3914.PubMedGoogle Scholar
  37. Cleaver, O., Tonissen, K., Saha, M., Krieg, P. (1997). Neovascularization of the Xenopus embryo. Dev Dyn 210:66–77.PubMedGoogle Scholar
  38. Clegg, C.H., Linkhart, T.A., Olwin, B.B., Hauschka, S.D. (1987). Growth factor control of skeletal muscle differentiation: commitment to terminal differentiation occurs in G1 phase and is repressed by fibroblast growth factor. J Cell Biol 105:949–956.PubMedGoogle Scholar
  39. Coffin, J.D., Florkiewicz, R.Z., Neumann, J., et al. (1995). Abnormal bone growth and selective translational regulation in basic fibroblast growth factor (FGF-2) transgenic mice. Mol Biol Cell 6:1861–1873.PubMedGoogle Scholar
  40. Coffin, J.D., Poole, T.J. (1988). Embryonic vascular development: immunohistochemical identification of the origin and subsequent morphogenesis of the major vessel primordia in quail embryos. Development 102:735–748.PubMedGoogle Scholar
  41. Coffin, J.D., Poole, T.J. (1991). Endothelial cell origin and migration in embryonic heart and cranial blood vessel development. Anat Rec 231:383–395.PubMedGoogle Scholar
  42. Conklin, D., Gilbertson, D., Taft, D.W., et al. (1999). Identification of a mammalian angiopoietin-related protein expressed specifically in liver. Genomics 62:477–482.PubMedGoogle Scholar
  43. Connolly, D.T., Heuvelman, D.M., Nelson, R., et al. (1989). Tumor vascular permeability factor stimulates endothelial cell growth and angiogenesis. J Clin Invest 84:1470–1478.PubMedGoogle Scholar
  44. Deindl, E., Fernández, B., Höfer, I.E., van Royen, N., Scholz, D., Schaper, W. (2000). Arteriogenesis, collateral blood vessels, and their development. In: Rubanyi, G.M., ed.Angiogenesis in health and disease pp. 31–46. New York: Marcell Dekker.Google Scholar
  45. De Lisser, H.M., Newman, P.J., Albelda, S.M. (1994). Molecular and functional aspects of PECAM-1/CD31. Immunology Today 15:490–495.Google Scholar
  46. De Ruiter, M.C., Hogers, B., Poelmann, R.E., Vanlperen, L., Gittenberger, D.G.A. (1991). The development of the vascular system in quail embryos: a combination of micro-vascular corrosion casts and immunohistochemical identification. Scanning Microsc 5: 1081–1089.Google Scholar
  47. De Ruiter, M.C., Poelmann, R.E., Mentink, M.M., Vaniperen, L., Gittenberger, D.G.A. (1993). Early formation of the vascular system in quail embryos. Anat Rec 235:261–274.Google Scholar
  48. Detmar, M., Brown, L., Schon, M., et al. (1998). Increased microvascular density and enhanced leukocyte rolling and adhesion in the skin of VEGF transgenic mice. J Invest Dermatol 111:1–6.PubMedGoogle Scholar
  49. De Vries, C., Escobedo, J.A., Ueno, H., Houck, K., Ferrara, N., Williams, L.T. (1992). The fms-like tyrosine kinase, a receptor for vasculare endothelial growth factor. Science 255: 989–991.PubMedGoogle Scholar
  50. Dickson, M., Martin, J., Cousins, F., Kulkarni, A., Karisson, S., Akhurst, R. (1995). Defective haematopoiesis and vasculogenesis in transforming growth factor-beta 1 knock out mice. Development 121:1845–1854.PubMedGoogle Scholar
  51. Dieterlen, L.F., Pardanaud, L., Yassine, F., Cormier, F. (1988). Early haemopoietic stem cells in the avian embryo. J Cell Sci Suppl 10:29–44.Google Scholar
  52. Drake, C.J., Little, C.D. (1995). Exogenous vascular endothelial growth factor induces malformed and hyperfused vessels during embryonic neovascularization. Proc Natl Acad Sci USA 92:7657–7661.PubMedGoogle Scholar
  53. Dumont, D.J., Fong, G.H., Puri, M.C., Gradwohl, G., Alitalo, K., Breitman, M.L. (1995). Vascularization of the mouse embryo-a study of Flk-1, Tek, Tie, and vascular endothelial growth factor expression during development. Dev Dyn 203:80–92.PubMedGoogle Scholar
  54. Dumont, D., Gradwohl, G., Fong, G., et al. (1994). Dominant-negative and targeted null mutations in the endothelial receptor tyrosine kinase, tek, reveal a critical role in vasculogenesis of the embryo. Genes Dev 8:1897–1909.PubMedGoogle Scholar
  55. Dumont, D.J., Jussila, L., Taipale, J., et al. (1998). Cardiovascular failure in mouse embryos deficient in VEGF receptor-3. Science 282:946–949.PubMedGoogle Scholar
  56. Ebert, B., Bunn, H. (1998). Regulation of transcription by hypoxia requires a multiprotein complex that includes hypoxia-inducible factor 1, an adjacent transcription factor, and p300/CREB binding protein. Mol Cell Biol 18:4089–4096.PubMedGoogle Scholar
  57. Eichmann, A., Corbel, C., Jaffredo, T., et al. (1998). Avian VEGF-C: cloning, embryonic expression pattern and stimulation of the differentiation of VEGFR2-expressing endothelial cell precursors. Development 125:743–752.PubMedGoogle Scholar
  58. Eichmann, A., Corbel, C., Nataf, V., Vaigot, P., Breant, C., Le Douarin, N. (1997). Ligand-dependent development of the endothelial and hemopoietic lineages from embryonic mesodermal cells expressing vascular endothelial growth factor receptor 2. Proc Natl Acad Sci USA 94:5141–5146.PubMedGoogle Scholar
  59. Eichmann, A., Marcelle, C., Breant, C., Le Douarin, N.M. (1993). Two molecules related to the VEGF receptor are expressed in early endothelial cells during avian embryonic development. Mech Dev 42:33–48.PubMedGoogle Scholar
  60. Ema, M., Hirota, K., Mimura, J., et al. (1999). Molecular mechanisms of transcription activation by HLF and HIF-lalpha in response to hypoxia: their stabilization and redox signal-induced interaction with CBP/p300. EMBO J 18:1905–1914.PubMedGoogle Scholar
  61. Ema, M., Taya, S., Yokotani, N., Sogawa, K., Matsuda, Y., Fujii-Kuriyama, Y. (1997). A novel bHLH-PAS factor with close sequence similarity to hypoxia-inducible factor-1 alpha regulates the VEGF expression and is potentially involved in lung and vascular development. Proc Natl Acad Sci USA 94:4273–4278.PubMedGoogle Scholar
  62. Esser, S., Wolburg, K., Wolburg, H., Breier, G., Kurzchalia, T., Risau, W. (1998). Vascular endothelial growth factor induces endothelial fenestrationsin vitro.J Cell Biol 140: 947–959.PubMedGoogle Scholar
  63. Evans, H.M. (1909). On the development of the aorta, cardinal and umbilical veins and the other blood vessels of vertebrate embryos from capillaries. Anat Rec 3:498–519.Google Scholar
  64. Farnebo, F., Piehl, F., Lagercrantz, J. (1999). Restricted expression pattern of vegf-d in the adult and fetal mouse: high expression in the embryonic lung. Biochem Biophys Res Commun 257:891–894.PubMedGoogle Scholar
  65. Feinberg, R.N., Noden, D.M. (1991). Experimental analysis of blood vessel development in the avian wing bud. Anat Rec 231:136–144.PubMedGoogle Scholar
  66. Feng, D., Nagy, J.A., Pyne, K., Hammel, I., Dvorak, H.F., Dvorak, A.M. (1999). Pathways of macromolecular extravasation across microvascular endothelium in response to VPF/VEGF and other vasoactive mediators. Microcirculation 6:23–44.PubMedGoogle Scholar
  67. Ferrara, N. (2000). The role of vascular endothelial growth factor in angiogenesis. In: Rubanyi, G.M., ed.Angiogenesis in health and diseasepp. 47–74. New York: Marcell Dekker. Ferrara, N., Carvermoore, K., Chen, H., et al. (1996). Heterozygous embryonic lethality induced by targeted inactivation of the VEGF Gene. Nature 380:439–442.Google Scholar
  68. Ferrara, N., Chen, H., Davis-Smyth, T., et al. (1998). Vascular endothelial growth factor is essential for corpus luteum angiogenesis. Nat Med 4:336–340.PubMedGoogle Scholar
  69. Flamme, I. (1989). Is extraembryonic angiogenesis in the chick embryo controlled by the endoderm? A morphology study. Anat Embryol Berl 180:259–272.PubMedGoogle Scholar
  70. Flamme, I., Breier, G., Risau, W. (1995a). Vascular endothelial growth factor (VEGF) and VEGF receptor 2 (flk-1) are expressed during vasculogenesis and vascular differentiation in the quail embryo. Dev Biol 169:699–712.Google Scholar
  71. Flamme, I., Fröhlich, T., Risau, W. (1997a). Molecular mechanisms of vasculogenesis and embryonic angiogenesis. J Cell Physiol 173:206–210.Google Scholar
  72. Flamme, I., Fröhlich, T., von Reutern, M., Kappel, A., Damert, A., Risau, W. (1997b). HRF, a putative basic helix-loop-helix-PAS-domain transcription factor is closely related to Hypoxia-inducible factor-la and developmentally expressed in blood vessels. Mech Dev 63:51–60.Google Scholar
  73. Flamme, I., Krieg, M., Plate, K.H. (1998). Up-regulation of vascular endothelial growth factor in stromal cells of hemangioblastomas is correlated with up-regulation of the transcription factor HRF/HIF-2alpha. Am J Pathol 153:25–29.PubMedGoogle Scholar
  74. Flamme, I., Risau, W. (1992). Induction of vasculogenesis and hematopoiesisin vitro.Development 116:435–439.PubMedGoogle Scholar
  75. Flamme, I., von Reutern, M., Drexler, H.C.A., Syed-Ali, S., Risau, W. (1995b). Over-expression of vascular endothelial growth factor in the avian embryo induces hypervascularization and increased vascular permeability without alterations of embryonic pattern formation. Dev Biol 171:399–414.Google Scholar
  76. Folkman, J., Shing, Y., (1992). Angiogenesis. J Biol Chem 267:10931–10934.PubMedGoogle Scholar
  77. Fong, G.H., Klingensmith, J., Wood, C.R., Rossant, J., Breitman, M.L., (1996). Regulation of flt-1 expression during mouse embryogenesis suggests a role in the establishment of vascular endothelium. Dev Dyn 207:1–10.PubMedGoogle Scholar
  78. Fong, G.H., Rossant, J., Gertsenstein, M., Breitman, M.L. (1995). Role of the flt-1 receptor tyrosine kinase in regulating the assembly of vascular endothelium. Nature 376:66–70.PubMedGoogle Scholar
  79. Forsythe, J.A., Jiang, B.H., Iyer, N.V., et al. (1996). Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1. Mol Cell Biol 16: 4604–4613.PubMedGoogle Scholar
  80. Fouquet, B., Weinstein, B., Serluca, F., Fishman, M. (1997). Vessel patterning in the embryo of the zebrafish: guidance by notochord. Dev Biol 183:37–48.PubMedGoogle Scholar
  81. Friesel, R.E., Maciag, T. (1995). Molecular mechanisms of angiogenesis: fibroblast growth factor signal transduction. FASEB J 9:919–925.PubMedGoogle Scholar
  82. Fujio, Y., Walsh, K. (1999). Akt mediates cytoprotection of endothelial cells by vascular endothelial growth factor in an anchorage-dependent manner. J Biol Chem 274:16349–16354.PubMedGoogle Scholar
  83. Fulgham, D.L., Widhalm, S.R., Martin, S., Coffin, J.D. (1999). FGF-2 dependent angiogenesis is a latent phenotype in basic fibroblast growth factor transgenic mice. Endothelium 6:185–195.PubMedGoogle Scholar
  84. Gerber, H.P., Condorelli, F., Park, J., Ferrara, N. (1997). 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 272:23659–23667.PubMedGoogle Scholar
  85. Gerber, H.P., Dixit, V., Ferrara, N. (1998). Vascular endothelial growth factor induces expression of the antiapoptotic proteins Bc1–2 and Al in vascular endothelial cells. J Biol Chem 273:13313–13316.PubMedGoogle Scholar
  86. Gerber, H.P., Hillan, K.J., Ryan, A.M., et al. (1999a). VEGF is required for growth and survival in neonatal mice. Development 126:1149–1159.Google Scholar
  87. Gerber, H.P., Vu, T.H., Ryan, A.M., Kowalski, J., Werb, Z., Ferrara, N. (1999b). VEGF couples hypertrophic cartilage remodeling, ossification and angiogenesis during endochondral bone formation. Nat Med 5:623–628.Google Scholar
  88. Gering, M., Rodaway, A.R., Gottgens, B., Patient, R.K., Green, A.R. (1998). The SCL gene specifies haemangioblast development from early mesoderm. EMBO J 17:4029–4045.PubMedGoogle Scholar
  89. Gnarra, J.R., Ward, J.M., Porter, F.D., et al. (1997). Defective placental vasculogenesis causes embryonic lethality in VHL-deficient mice. Proc Natl Acad Sci USA 94:9102–9107.PubMedGoogle Scholar
  90. Gonzalez Crussi, F. (1971). Vasculogenesis in the chick embryo. An ultrastructural study.Am J Anat 130:441–460.Google Scholar
  91. Grosios, K., Leek, J.P., Markham, A.F., Yancopoulos, G.D., Jones, P.F. (1999). Assignment of ANGPT4, ANGPT1, and ANGPT2 encoding angiopoietins 4,1 and 2 to human chromosome bands 20p13, 8g22.3->q23 and 8p23.1, respectively, byin situhybridization and radiation hybrid mapping. Cytogenet Cell Genet 84:118–120.PubMedGoogle Scholar
  92. Haar, J.L., Ackerman, G. (1971). A phase and electron microscopic study of vasculogenesis and erythropoiesis in the yolk sac of the mouse. Anat Rec 170:199–224.PubMedGoogle Scholar
  93. Henkemeyer, M., Rossi, D.J., Holmyard, D.P., et al. (1995). Vascular system defects and neuronal apoptosis in mice lacking ras GTPase-activating protein. Nature 377:695–701.PubMedGoogle Scholar
  94. Hidaka, M., Stanford, W.L., Bernstein, A. (1999). Conditional requirement for the Flk-1 receptor in thein vitrogeneration of early hematopoietic cells. Proc Natl Acad Sci USA 96:7370–7375.PubMedGoogle Scholar
  95. Hirakow, R., Hiruma, T. (1981). Scanning electron microscopic study on the development of primitive blood vessels in chick embryos at the early somite-stage. Anat Embryol Berl 163:299–306.PubMedGoogle Scholar
  96. Hirakow, R., Hiruma, T. (1983). TEM-studies on development and canalization of the dorsal aorta in the chick embryo. Anat Embryol Berl 166:307–315.PubMedGoogle Scholar
  97. Hirashima, M., Kataoka, H., Nishikawa, S., Matsuyoshi, N., Nishikawa, S. (1999). Maturation of embryonic stem cells into endothelial cells in anin vitromodel of vasculogenesis. Blood 93:1253–1263.PubMedGoogle Scholar
  98. Hiratsuka, S., Minowa, O., Kuno, J., Noda, T., Shibuya, M. (1998). Flt-1 lacking the tyrosine kinase domain is sufficient for normal development and angiogenesis in mice. Proc Natl Acad Sci USA 95:9349–9354.PubMedGoogle Scholar
  99. His, W. (1900). Lecithoblast and Angioblast der Wirbelthiere. Abhandl K S Ges Wiss MathPhys 22:171–328.Google Scholar
  100. Hogenesch, J.B., Chan, W.K., Jackiw, V.H., et al. (1997). Characterization of a subset of the basic-helix-loop-helix-PAS superfamily that interacts with components of the dioxin signaling pathway. J Biol Chem 272:8581–8593.PubMedGoogle Scholar
  101. Holder, N., Klein, R. (1999). Eph receptors and ephrins: effectors of morphogenesis. Development 126:2033–2044.PubMedGoogle Scholar
  102. Holland, S., Gale, N., Mbamalu, G., Yancopoulos, G., Henkemeyer, M., Pawson, T. (1996). Bidirectional signalling through the EPH-family receptor Nuk and its transmembrane ligands. Nature 383:722–725.PubMedGoogle Scholar
  103. Hoper, J., Jahn, H. (1995). Influence of environmental oxygen concentration on growth and vascular density of the area vasculosa in chick embryos. Int J Microcirc Clin Exp 15:186–192.PubMedGoogle Scholar
  104. Houck, K.A., Ferrara, N., Winer, J., Cachianes, G., Li, B., Leung, D.W. (1991). The vascular endothelial growth factor family: identification of a fourth molecular species and characterization of alternative splicing of RNA. Mol Endocrinol 5:1806–1814.PubMedGoogle Scholar
  105. Huang, L., Gu, J., Schau, M., Bunn, H. (1998). Regulation of hypoxia-inducible factor 1 alpha is mediated by an 02-dependent degradation domain via the ubiquitin-proteasome pathway. Proc Natl Acad Sci USA 95:7987–7992.PubMedGoogle Scholar
  106. Hughes, A. (1935). Studies on the area vasculosa of the embryo chick. I. The first differentiation of the vitellina arteria. J Anat 70:76–122.PubMedGoogle Scholar
  107. Husmann, I., Soulet, L., Gautron, J., Martelly, I., Barritault, D. (1996). Growth factors in skeletal muscle regeneration. Cytokine Growth Factor Rev 7:249–258.PubMedGoogle Scholar
  108. Ikeda, E., Achen, M.G., Breier, G., Risau, W. (1995). Hypoxia-induced transcriptional activation and increased mRNA stability of vascular endothelial growth factor in C6 glioma cells. J Biol Chem 270:19761–19766.PubMedGoogle Scholar
  109. Isaac, D.D., Andrew, D.J. (1996). Tubulogenesis in drosophila-a requirement for the trachealess gene product. Genes Dev 10:103–117.PubMedGoogle Scholar
  110. Isner, J.M., Asahara, T. (2000). Therapeutic angiogenesis. In: Rubanyi, G.M., ed.Angiogenesis in health and diseasepp. 489–518. New York: Marcell Dekker.Google Scholar
  111. Iyer, N.V., Kotch, L.E., Agani, F., et al. (1998). Cellular and developmental control of 02homeostasis by hypoxia-inducible factor 1 alpha. Genes Dev 12:149–162.PubMedGoogle Scholar
  112. Jaffredo, T., Gautier, R., Eichmann, A., Dieterlen-Lievre, F. (1998). Intraaortic hemopoietic cells are derived from endothelial cells during ontogeny. Development 125:4575–4583.PubMedGoogle Scholar
  113. Jakeman, L.B., Winer, J., Bennett, G.L., Altar, C.A., Ferrara, N. (1992). Binding sites for vascular endothelial growth factor are localized on endothelial cells in adult rat tissues. J Clin Invest 89:244–253.PubMedGoogle Scholar
  114. Jeltsch, M., Kaipainen, A., Joukov, V., et al. (1997). Hyperplasia of lymphatic vessels in VEGF-C transgenic mice. Science 276:1423–1425.PubMedGoogle Scholar
  115. Joukov, V., Pajusola, K., Kaipainen, A., et al. (1996). A novel vascular endothelial growth factor, VEGF-C, is a ligand for the Flt4 (VEGFR-3) and KDR (VEGFR-2) receptor tyrosine kinases EMBO J 15:290–298.Google Scholar
  116. Kaipainen, A., Korhonen, J., Mustonen, T., et al. (1995). Expression of the fms-like tyrosine kinase 4 gene becomes restricted to lymphatic endothelium during development. Proc Natl Acad Sci USA 92:3566–3570.PubMedGoogle Scholar
  117. Kallio, P.J., Wilson, W.J., O’Brien, S., Makino, Y., Poellinger, L. (1999). Regulation of the hypoxia-inducible transcription factor lalpha by the ubiquitin-proteasome pathway. J Biol Chem 274:6519–6525.PubMedGoogle Scholar
  118. Kappel, A., Ronicke, V., Damert, A., Flamme, I., Risau, W., Breier, G. (1999). Identification of vascular endothelial growth factor (VEGF) receptor-2 (Flk-1) promoter/enhancer sequences sufficient for angioblast and endothelial cell-specific transcription in transgenic mice. Blood 93:4284–4292.PubMedGoogle Scholar
  119. Kawasaki, T., Kitsukawa, T., Bekku, Y., et al. (1999). A requirement for neuropilin-1 in embryonic vessel formation. Development 126:4895–4902.PubMedGoogle Scholar
  120. Kendall, R.L., Wang, G., Thomas, K.A. (1996). Identification of a natural soluble form of the vascular endothelial growth factor receptor, Flt-1, and its heterodimerization with KDR. Biochem Biophys Res Commun 226:324–328.PubMedGoogle Scholar
  121. Kenyon, B.M., Voest, E.E., Chen, C.C., Flynn, E., Folkman, J., D’Amato, R.J. (1996). A model of angiogenesis in the mouse cornea. Invest Ophthalmol Vis Sci 37:1625–1632.PubMedGoogle Scholar
  122. Kessel, J., Fabian, B. (1985). Graded morphogenetic patterns during the development of the extraembryonic blood system and coelom of the chick blastoderm: a scanning electron microscope and light microscope study. Am J Anat 173:99–112.PubMedGoogle Scholar
  123. Kitsukawa, T., Shimono, A., Kawakami, A., Kondoh, H., Fujisawa, H. (1995). Over-expression of a membrane protein, neuropilin, in chimeric mice causes anomalies in the cardiovascular system, nervous system and limbs. Development 121:4309–4318.PubMedGoogle Scholar
  124. Koblizek, T., Weiss, C., Yancopoulos, G., Deutsch, U., Risau, W. (1998). Angiopoietin-1 induces sprouting angiogenesisin vitro.Curr Biol 8:529–532.PubMedGoogle Scholar
  125. Kotch, L.E., Iyer, N.V., Laughner, E., Semenza, G.L. (1999). Defective vascularization of HIF-lalpha-null embryos is not associated with VEGF deficiency but with mesenchymal cell death. Dev Biol 209:254–267.PubMedGoogle Scholar
  126. Kozak, K.R., Abbott, B., Hankinson, O. (1997). ARNT-deficient mice and placental differentiation. Dev Biol 191:297–305.PubMedGoogle Scholar
  127. Krah, K., Mironow, V., Risau, W., Flamme, I. (1994). Induction of vasculogenesis in quail blastodisc derived embryoid bodies. Dev Biol 164:123–132.PubMedGoogle Scholar
  128. Kremer, C., Breier, G., Risau, W., Plate, K.H. (1997). Up-regulation of flk-1/vascular endothelial growth factor receptor 2 by its ligand in a cerebral slice culture system. Cancer Res 57:3852–3859.PubMedGoogle Scholar
  129. Kukk, E., Lymboussaki, A., Taira, S., et al. (1996). VEGF-C receptor binding and pattern of expression with VEGFR-3 suggests a role in lymphatic vascular development. Development 122:3829–3837.PubMedGoogle Scholar
  130. Kurz, H., Gartner, T., Eggli, P., Christ, B. (1996). First blood vessels in the avian neural tube are formed by a combination of dorsal angioblast immigration and ventral sprouting of endothelial cells. Dev Biol Vol 176:133–147.Google Scholar
  131. Labastie, M.C., Poole, T.J., Peault, B.M., Le Douarin, N.M. (1986). MB1, a quail leukocyte-endothelium antigen: partial characterization of the cell surface and secreted forms in cultured endothelial cells. Proc Natl Acad Sci USA 83:9016–9020.PubMedGoogle Scholar
  132. Lamoreaux, W.J., Fitzgerald, M.E., Reiner, A., Hasty, K.A., Charles, S.T. (1998). Vascular endothelial growth factor increases release of gelatinase A and decreases release of tissue inhibitor of metalloproteinases by microvascular endothelial cellsin vitro.Microvasc Res 55:29–42.PubMedGoogle Scholar
  133. Lanot, R. (1980). Formation of the early vascular network in chick embryo: microscopical aspects. Arch Biol Liege 91:423–438.PubMedGoogle Scholar
  134. Larcher, F., Murillas, R., Bolontrade, M., Conti, C., Jorcano, J. (1998). VEGF/VPF over-expression in skin of transgenic mice induces angiogenesis, vascular hyperpermeability and accelerated tumor development. Oncogene 17:303–311.PubMedGoogle Scholar
  135. Leung, D.W., Cachianes, G., Kuang, W.J., Goeddel, D.V., Ferrara, N. (1989). Vascular endothelial growth factor is a secreted angiogenic mitogen. Science 246:1306–1309.PubMedGoogle Scholar
  136. Levy, A.P., Levy, N.S., Wegner, S., Goldberg, M.A. (1995). Transcriptional regulation of the rat vascular endothelial growth factor gene by hypoxia. J Biol Chem 270:13333–13340.PubMedGoogle Scholar
  137. Liao, E., Paw, B., Oates, A., Pratt, S., Postlethwait, J., Zon, L. (1998). SCL/Tal-1 transcription factor acts downstream of cloche to specify hematopoietic and vascular progenitors in zebrafish. Genes Dev 12:621–626.PubMedGoogle Scholar
  138. Liao, W., Bisgrove, B., Sawyer, H., et al. (1997). The zebrafish gene cloche acts upstream of a flk-1 homologue to regulate endothelial cell differentiation. Development 124:381–389.PubMedGoogle Scholar
  139. Lindahl, P., Johansson, B., Leveen, P., Betsholtz, C. (1997). Pericyte loss and microaneurysm formation in PDGF-B-deficient mice. Science 277:242–245.PubMedGoogle Scholar
  140. Lu, M., Perez, V.L., Ma, N., et al. (1999). VEGF increases retinal vascular ICAM-1 expressionin vivo.Invest Ophthalmol Vis Sci 40:1808–1812.PubMedGoogle Scholar
  141. Maglione, D., Guerriero, V., Viglietto, G., Delli Bovi, P., Persico, M.G. (1991). Isolation of a human placenta cDNA coding for a protein related to the vascular permeability factor. Proc Natl Acad Sci USA 88:9267–9271.PubMedGoogle Scholar
  142. Maisonpierre, P., Suri, C., Jones, P., et al. (1997). Angiopoietin-2, a natural antagonist for Tie2 that disruptsin vivoangiogenesis. Science 277:55–60.PubMedGoogle Scholar
  143. Makinen, T., Olofsson, B., Karpanen, T., et al. (1999). Differential binding of vascular endothelial growth factor B splice and proteolytic isoforms to neuropilin-1. J Biol Chem 274:21217–21222.PubMedGoogle Scholar
  144. Maltepe, E., Schmidt, J.V., Baunoch, D., Bradfield, C.A., Simon, M.C. (1997). Abnormal angiogenesis and responses to glucose and oxygen deprivation in mice lacking the protein ARNT. Nature 386:403–407.PubMedGoogle Scholar
  145. Manning, G., Krasnow, M. (1993). Development of the Drosophila tracheal system. In:The Development of Drosophila melanogasterpp. 609–685. Cold Spring Harbor NY: Cold Spring Harbor Laboratory Press.Google Scholar
  146. Marti, H.H., Risau, W. (1998). Systemic hypoxia changes the organ-specific distribution of vascular endothelial growth factor and its receptors. Proc Natl Acad Sci USA 95: 15809–15814.PubMedGoogle Scholar
  147. Mato, M., Aikawa, E., Kishi, K. (1964). Some observations on interstice between mesoderm and endoderm in the area vasculosa of chick blastoderm. Exp Cell Res 35:426–428.PubMedGoogle Scholar
  148. Maxwell, P.H., Wiesener, M.S., Chang, G.W., et al. (1999). The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis. Nature 399:271–275.PubMedGoogle Scholar
  149. McGann, J., Silver, L., Liesveld, J., Palis, J. (1997). Erythropoietin-receptor expression and function during the initiation of murine yolk sac erythropoiesis. Exp Hematol 25:1149–1157.PubMedGoogle Scholar
  150. Medvinsky, A., Dzierzak, E. (1996). Definitive hematopoiesis is autonomously initiated by the AGM region. Cell 86:897–906.PubMedGoogle Scholar
  151. Meyer, M., Clauss, M., Lepple-Wienhues, A., et al. (1999). A novel vascular endothelial growth factor encoded by Orf virus, VEGF-E, mediates angiogenesis via signalling through VEGFR-2 (KDR) but not VEGFR-1 (Flt-1) receptor tyrosine kinases. EMBO J 18:363–374.PubMedGoogle Scholar
  152. Miao, H.Q., Soker, S., Feiner, L., Alonso, J.L., Raper, J.A., Klagsbrun, M. (1999). 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 146:233–242.PubMedGoogle Scholar
  153. Michel, C.C., Neal, C.R. (1999). Openings through endothelial cells associated with increased microvascular permeability. Microcirculation 6:45–54.PubMedGoogle Scholar
  154. Migdal, M., Huppertz, B., Tessler, S., et al. (1998). Neuropilin-1 is a placenta growth factor-2 receptor. J Biol Chem 273:22272–22278.PubMedGoogle Scholar
  155. Mikawa, T., Fischman, D.A. (1992). Retroviral analysis of cardiac morphogenesis: discontinuous formation of coronary vessels. Proc Natl Acad Sci USA 89:9504–9508.PubMedGoogle Scholar
  156. Millauer, B., Wizigmann Voos, S., Schnurch, H., et al. (1993). High affinity VEGF binding and developmental expression suggest Flk-1 as a major regulator of vasculogenesis and angiogenesis. Cell 72:835–846.PubMedGoogle Scholar
  157. Miquerol, L., Gertsenstein, M., Harpal, K., Rossant, J., Nagy, A. (1999). Multiple develop-mental roles of VEGF suggested by a LacZ-tagged allele. Dev Biol 212:307–322.PubMedGoogle Scholar
  158. Miura, Y., Wilt, F.H. (1969). Tissue interaction and the formation of the first erythroblasts of the chick embryo. Dev Biol 19:201–211.PubMedGoogle Scholar
  159. Monacci, W.T., Merrill, M.J., Oldfield, E.H. (1993). Expression of vascular permeability factor/vascular endothelial growth factor in normal rat tissues. Am J Physiol 264: C995–1002.PubMedGoogle Scholar
  160. Munoz-Chapuli, R., Perez-Pomares, J.M., Macias, D., Garcia-Garrido, L., Carmona, R., Gonzalez, M. (1999). Differentiation of hemangioblasts from embryonic mesothelial cells? A model on the origin of the vertebrate cardiovascular system. Differentiation 64: 133–141.PubMedGoogle Scholar
  161. Murphy, M.E., Carlson, E.C. (1978). An ultrastructural study of developing extracellular matrix in vitelline blood vessels of the early chick embryo. Am J Anat 151:345–375.PubMedGoogle Scholar
  162. Murray, P.D.F. (1932). The developmentin vitroof the blood of the early chick embryo. R Soc London (Ser B III).Google Scholar
  163. Nehls, V., Drenckhahn, D. (1995). A novel, microcarrier-basedin vitroassay for rapid and reliable quantification of three-dimensional cell migration and angiogenesis. Microvasc Res 50:311–322.PubMedGoogle Scholar
  164. Nishikawa, S., Nishikawa, S., Hirashima, M., Matsuyoshi, N., Kodama, H. (1998). Progressive lineage analysis by cell sorting and culture identifies FLK1+VE-cadherin+ cells at a diverging point of endothelial and hemopoietic lineages. Development 125:1747–1757.PubMedGoogle Scholar
  165. Noden, D.M. (1989). Embryonic origins and assembly of blood vessels. Am Rev Respir Dis 140:1097–1103.PubMedGoogle Scholar
  166. Nor, J.E., Christensen, J., Mooney, D.J., Polverini, P.J. (1999). Vascular endothelial growth factor (VEGF)-mediated angiogenesis is associated with enhanced endothelial cell survival and induction of Bcl- 2 expression. Am J Pathol 154:375–384.PubMedGoogle Scholar
  167. North, T., Gu, T.L., Stacy, T., et al. (1999). Cbfa2 is required for the formation of intraaortic hematopoietic clusters. Development 126:2563–2575.PubMedGoogle Scholar
  168. Ogawa, S., Oku, A., Sawano, A., Yamaguchi, S., Yazaki, Y., Shibuya, M. (1998). A novel type of vascular endothelial growth factor, VEGF-E (NZ-7 VEGF), preferentially utilizes KDR/Flk-1 receptor and carries a potent mitotic activity without heparin-binding domain. J Biol Chem 273:31273–31282.PubMedGoogle Scholar
  169. Ogunshola, O.O., Stewart, W.B., Mihalcik, V., Solli, T., Madri, J.A., Ment, L.R. (2000). Neuronal VEGF expression correlates with angiogenesis in postnatal developing rat brain. Brain Res Dev Brain Res 119:139–153.PubMedGoogle Scholar
  170. Oh, H., Takagi, H., Suzuma, K., Otani, A., Matsumura, M., Honda, Y. (1999). Hypoxia and vascular endothelial growth factor selectively up-regulate angiopoietin-2 in bovine microvascular endothelial cells. J Biol Chem 274:15732–15739.PubMedGoogle Scholar
  171. Oike, Y., Takakura, N., Hata, A., et al. (1999). Mice homozygous for a truncated form of CREB-binding protein exhibit defects in hematopoiesis and vasculo-angiogenesis. Blood 93:2771–2779.PubMedGoogle Scholar
  172. Okada, H., Watanabe, T., Niki, M., et al. (1998). AML1(-/-) embryos do not express certain hematopoiesis-related gene transcripts including those of the PU.1 gene. Oncogene 17: 2287–2293.PubMedGoogle Scholar
  173. Okamoto, N., Tobe, T., Hackett, S.F., et al. (1997). Transgenic mice with increased expression of vascular endothelial growth factor in the retina: a new model of intraretinal and subretinal neovascularization. Am J Pathol 151:281–291.PubMedGoogle Scholar
  174. Olah, I., Medgyes, J., Glick, B. (1988). Origin of aortic cell clusters in the chicken embryo. Anat Rec 222:60–68.PubMedGoogle Scholar
  175. Olofsson, B., Korpelainen, E., Pepper, M.S., et al. (1998). 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 95:11709–11714.PubMedGoogle Scholar
  176. Pandey, A., Shao, H., Marks, R., Polverini, R, Dixit, V. (1995). Role of B61, the ligand for the Eck receptor tyrosine kinase, in TNF-alpha-induced angiogenesis. Science 268: 567–569.PubMedGoogle Scholar
  177. Pardanaud, L., Altmann, C., Kitos, P., Dieterlen, L.F., Buck, C.A. (1987). Vasculogenesis in the early quail blastodisc as studied with a monoclonal antibody recognizing endothelial cells. Development 100:339–349.PubMedGoogle Scholar
  178. Pardanaud, L., Dieterlen-Lievre, F. (1999). Manipulation of the angiopoietic/hemangiopoietic commitment in the avian embryo. Development 126:617–627.PubMedGoogle Scholar
  179. Pardanaud, L., Luton, D., Prigent, M., Bourcheix, L., Catala, M., Dieterlen-Lièvre, F. (1996). Two distinct endothelial lineages in ontogeny, one of them related to hemopoiesis. Development 122:1363–1371.PubMedGoogle Scholar
  180. Pardanaud, L., Yassine, F., Dieterlen, L.F. (1989). Relationship between vasculogenesis, angiogenesis and haemopoiesis during avian ontogeny. Development 105:473–485.PubMedGoogle Scholar
  181. Parker, L., Stainier, D.Y. (1999). Cell-autonomous and non-autonomous requirements for the zebrafish gene cloche in hematopoiesis. Development 126:2643–2651.PubMedGoogle Scholar
  182. Patstone, G., Pasquale, E.B., Maher, P. (1993). Different members of the fibroblast growth factor receptor family are specific to distinct cell types in the developing chicken embryo. Dev Biol 155:107–123.PubMedGoogle Scholar
  183. Peault, B.M., Thiery, J.P., Le Douarin, N.M. (1983). Surface marker for hemopoietic and endothelial cell lineages in quail that is defined by a monoclonal antibody. Proc Natl Acad Sci USA 80:2976–2980.PubMedGoogle Scholar
  184. Peters, K.G., Werner, S., Chen, G., Williams, L.T. (1992). Two FGF receptor genes are differentially expressed in epithelial and mesenchymal tissues during limb formation and organogenesis in the mouse. Development 114:233–243.PubMedGoogle Scholar
  185. Petrova, T.V., Makinen, T., Alitalo, K. (1999). Signaling via vascular endothelial growth factor receptors. Exp Cell Res 253:117–130.PubMedGoogle Scholar
  186. Phillips, G.D., Stone, A.M., Jones, B.D., Schultz, J.C., Whitehead, R.A., Knighton, D.R. (1994). Vascular endothelial growth factor (rhVEGF165) stimulates direct angiogenesis in the rabbit cornea.In Vivo8:961–965.PubMedGoogle Scholar
  187. Plate, K., Breier, G., Millauer, B., Ullrich, A., Risau, W. (1993). Up-regulation of vascular endothelial growth factor and its cognate receptors in a rat glioma model of tumor angiogenesis. Cancer Res 53:5822–5827.PubMedGoogle Scholar
  188. Plate, K.H., Breier, G., Weich, H.A., Mennel, H.D., Risau, W. (1994). Vascular endothelial growth factor and glioma angiogenesis-coordinate induction of VEGF receptors, distribution of VEGF protein and possiblein vivoregulatory mechanisms. Int J Cancer 59:520–529.PubMedGoogle Scholar
  189. Plate, K.H., Breier, G., Weich, H.A., Risau, W. (1992). Vascular endothelial growth factor is a potential tumour angiogenesis factor in human gliomasin vivo.Nature 359:845–848.PubMedGoogle Scholar
  190. Poole, T.J., Coffin, J.D. (1989). Vasculogenesis and angiogenesis: two distinct morpho-genetic mechanisms establish embryonic vascular pattern. J Exp Zool 251:224–231.PubMedGoogle Scholar
  191. Porcher, C., Swat, W., Rockwell, K., Fujiwara, Y., Alt, F.W., Orkin, S.H. (1996). The T cell leukemia oncoprotein SCL/tal-1 is essential for development of all hematopoietic lineages. Cell 86:47–57.PubMedGoogle Scholar
  192. Quinn, T.P., Peters, K.G., De, V.C., Ferrara, N., Williams, L.T. (1993). Fetal liver kinase 1 is a receptor for vascular endothelial growth factor and is selectively expressed in vascular endothelium. Proc Natl Acad Sci USA 90:7533–7537.PubMedGoogle Scholar
  193. Rich, I. (1995). Primordial germ cells are capable of producing cells of the hematopoietic systemin vitro.Blood 15:463–472.Google Scholar
  194. Riley, B.B., Savage, M.P., Simandl, B.K., Olwin, B.B., Fallon, J.F. (1993). Retroviral expression of FGF-2 (bFGF) affects patterning in chick limb bud. Development 118:95–104. Risau, W. (1997). Mechanisms of angiogenesis. Nature 386:671–674.Google Scholar
  195. Risau, W., Flamme, I. (1995). Vasculogenesis. Annu Rev Cell Dev Biol 11:73–91.PubMedGoogle Scholar
  196. Roberts, W.G., Palade, G.E. (1995). Increased microvascular permeability and endothelial fenestration induced by vascular endothelial growth factor. J Cell Sci 108:2369–2379.PubMedGoogle Scholar
  197. Robertson, P.L., Du Bois, M., Bowman, P.D., Goldstein, G.W. (1985). Angiogenesis in developing rat brain: anin vivoandin vitrostudy. Brain Res 355:219–223.PubMedGoogle Scholar
  198. Ryan, H.E., Lo, J., Johnson, R.S. (1998). HIF-1 alpha is required for solid tumor forma-tion and embryonic vascularization. Embo J 17:3005–3015.PubMedGoogle Scholar
  199. Sabin, F.R. (1917). Origin and development of the primitive vessels of the chick and of the pig. Carnergie Contrib Embryol 6:61–124.Google Scholar
  200. Sabin, F.R. (1920). Preliminary note on the differentiation of angioblasts and the method by which they produce blood-vessels, blood plasma and red blood-cells as seen in the living chick. Anat Rec 13:199–204.Google Scholar
  201. Sato, A., Iwama, A., Takakura, N., Nishio, H., Yancopoulos, G., Suda, T. (1998). Characterization of TEK receptor tyrosine kinase and its ligands, angiopoietins, in human hematopoietic progenitor cells. Int Immunol 10:1217–1227.PubMedGoogle Scholar
  202. Sato, T.N., Tozawa, Y., Deutsch, U., et al. (1995). Distinct roles of the receptor tyrosine kinases Tie-1 and Tie-2 in blood vessel formation. Nature 376:70–74.PubMedGoogle Scholar
  203. Schmidt, M., Flamme, I. (1998). Thein vivoactivity of vascular endothelial growth factor isoforms in the avian embryo. Growth Factors 15:183–197.PubMedGoogle Scholar
  204. Schwartz, S.M., Benditt, E.P. (1977). Aortic endothelial cell replication.I. Effects of age and hypertension in the rat. Circ Res 41:248–255.PubMedGoogle Scholar
  205. Shalaby, F., Rossant, J., Yamaguchi, T.P., et al. (1995). Failure of blood-island formation and vasculogenesis in Flk-l-deficient mice. Nature 376:62–66.PubMedGoogle Scholar
  206. Shivdasani, R., Mayer, E., Orkin, S. (1995). Absence of blood formation in mice lacking the T-cell leukaemia oncoprotein tal-1/SCL. Nature 373:432–434.PubMedGoogle Scholar
  207. Shweiki, D., Itin, A., Soffer, D., Keshet, E. (1992). Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis. Nature 359:843–845.PubMedGoogle Scholar
  208. Shweiki, D., Neeman, M., Itin, A., Keshet, E. (1995). Induction of vascular endothelial growth factor expression by hypoxia and by glucose deficiency in multicell spheroids-implications for tumor angiogenesis. Proc Natl Acad Sci USA 92:768–772.PubMedGoogle Scholar
  209. Slack, J.M., Darlington, B.G., Heath, J.K., Godsave, S.F. (1987). Mesoderm induction in early Xenopus embryos by heparin-binding growth factors. Nature 326:197–200.PubMedGoogle Scholar
  210. Soker, S., Takashima, S., Miao, H.Q., Neufeld, G., Klagsbrun, M. (1998). Neuropilin-1 is expressed by endothelial and tumor cells as an isoform-specific receptor for vascular endothelial growth factor. Cell 92:735–745.PubMedGoogle Scholar
  211. Stein, E., Lane, A., Cerretti, D., et al. (1998). Eph receptors discriminate specific ligand oligomers to determine alternative signaling complexes, attachment, and assembly responses. Genes Dev 12:667–678.PubMedGoogle Scholar
  212. Stolen, C.M., Jackson, M.W., Griep, A.E. (1997). Overexpression of FGF-2 modulates fiber cell differentiation and survival in the mouse lens. Development 124:4009–4017.PubMedGoogle Scholar
  213. Stone, J., Itin, A., Alon, T., et al. (1995). Development of retinal vasculature is mediated by hypoxia-induced vascular endothelial growth factor (VEGF) expression by neuroglia. J Neurosci 15:4738–4747.PubMedGoogle Scholar
  214. Stratmann, A., Risau, W., Plate, K.H. (1998). Cell type-specific expression of angiopoietin1 and angiopoietin-2 suggests a role in glioblastoma angiogenesis. Am J Pathol 153:14591466.Google Scholar
  215. Sumoy, L., Keasey, J., Dittman, T., Kimelman, D. (1997). A role for notochord in axial vascular development revealed by analysis of phenotype and the expression of VEGR-2 in zebrafish flh and ntl mutant embryos. Mech Dev 63:15–27.PubMedGoogle Scholar
  216. Suri, C., Jones, P.F., Patan, S., et al. (1996). Requisite role of angiopoietin-1, a ligand for the tie2 receptor, during early embryonic angiogenesis. Cell 87:1171–1180.PubMedGoogle Scholar
  217. Suri, C., McClain, J., Thurston, G., et al. (1998). Increased vascularization in mice overexpressing angiopoietin-1. Science 282:468–471.PubMedGoogle Scholar
  218. Takeshita, S., Tsurumi, Y., Couffinahl, T., et al. (1996). Gene transfer of naked DNA encoding for three isoforms of vascular endothelial growth factor stimulates collateral developmentin vivo.Lab Invest 75:487–501.PubMedGoogle Scholar
  219. Takeshita, S., Zheng, L.P., Brogi, E., et al. (1994). Therapeutic angiogenesis. A single intraarterial bolus of vascular endothelial growth factor augments revascularization in a rabbit ischemic hind limb model. J Clin Invest 93:662–670.PubMedGoogle Scholar
  220. Tavian, M., Coulombel, L., Luton, D., San Clemente, H., Dieterlen-Lièvre, F., Péault, B.1992 Aorta-associated CD34+ hematopoietic cells in the early human embryo. Blood 87:67–72.Google Scholar
  221. Terman, B.I., Dougher Vermazen, M., Carrion, M.E., et al. (1992). Identification of the KDR tyrosine kinase as a receptor for vascular endothelial cell growth factor. Biochem Biophys Res Commun 187:1579–1586.PubMedGoogle Scholar
  222. Terman, B.I., Khandke, L., Doughervermazan, M., et al. (1994). VEGF receptor subtypes kdr and fltl show different sensitivities to heparin and placenta growth factor. Growth Factors 11:187–195.PubMedGoogle Scholar
  223. Thompson, J., Slack, J.M.W. (1992). Over-expression of fibroblast growth factors in Xenopus embryos. Mech Dev 38:175–182.PubMedGoogle Scholar
  224. Thurston, G., Suri, C., Smith, K., et al. (1999). Leakage-resistant blood vessels in mice transgenically overexpressing angiopoietin-1. Science 286:2511–2514.PubMedGoogle Scholar
  225. Tian, H., Hammer, R.E., Matsumoto, A.M., Russell, D.W., McKnight, S.L. (1998). The hypoxia-responsive transcription factor EPAS1 is essential for catecholamine homeostasis and protection against heart failure during embryonic development. Genes Dev 12: 3320–3324.PubMedGoogle Scholar
  226. Tian, H., McKnight, S.L., Russell, D.W. (1997). Endothelial PAS domain protein 1 (EPAS1), a transcription factor selectively expressed in endothelial cells. Genes Dev 11:7282.Google Scholar
  227. Tischer, E., Gospodarowicz, D., Mitchell, R., et al. (1989). Vascular endothelial growth factor: a new member of the platelet-derived growth factor gene family. Biochem Biophys Res Commun 165:1198–1206.PubMedGoogle Scholar
  228. Tomanek, R.J., Ratajska, A., Kitten, G.T., Yue, X., Sandra, A. (1999). Vascular endothelial growth factor expression-coincides with coronary vasculogenesis and angiogenesis. Dev Dyn 215:54–61.PubMedGoogle Scholar
  229. Tran, J., Rak, J., Sheehan, C., et al. (1999). Marked induction of the IAP family antiapoptotic proteins survivin and XIAP by VEGF in vascular endothelial cells. Biochem Biophys Res Commun 264:781–788.PubMedGoogle Scholar
  230. Tuder, R.M., Flook, B.E., Voelkel, N.F. (1995). Increased gene expression for VEGF and the VEGF receptors KDR/Flk and Flt in lungs exposed to acute or to chronic hypoxia. Modulation of gene expression by nitric oxide. J Clin Invest 95:1798–1807.PubMedGoogle Scholar
  231. Unemori, E.N., Ferrara, N., Bauer, E.A., Amento, E.P. (1992). Vascular endothelial growth-factor induces interstitial collagenase expression in human endothelial-cells. J Cell Physiol 153:557–562.PubMedGoogle Scholar
  232. Valenzuela, D.M., Griffiths, J.A., Rojas, J., et al. (1999). Angiopoietins 3 and 4: diverging gene counterparts in mice and humans. Proc Natl Acad Sci USA 96:1904–1909.PubMedGoogle Scholar
  233. Visvader, J., Fujiwara, Y., Orkin, S. (1998). Unsuspected role for the T-cell leukemia protein SCL/tal-1 in vascular development. Genes Dev 12:473–479.PubMedGoogle Scholar
  234. Waltenberger, J., Claesson-Welsh, L., Siegbahn, A., Shibuya, M., Heldin, C.H. (1994). Different signal transduction properties of KDR and Fltl, two receptors for vascular endothelial growth factor. J Biol Chem 269:26988–26995.PubMedGoogle Scholar
  235. Wang, G.L., Jiang, B.H., Rue, E.A., Semenza, G.L. (1995). Hypoxia inducible factor 1 is a basic helix loop helix PAS heterodimer regulated by cellular 02tension. Proc Nail Acad Sci USA 92:5510–5514.Google Scholar
  236. Wang, H., Chen, Z., Anderson, D. (1998). Molecular distinction and angiogenic interaction between embryonic arteries and veins revealed by ephrin-B2 and its receptor Eph-B4. Cell 93:741–753.PubMedGoogle Scholar
  237. Weinstein, B.M. (1999). What guides early embryonic blood vessel formation? Dev Dyn 215:2–11.PubMedGoogle Scholar
  238. Wenger, R.H., Gassmann, M. (1997). Oxygen(es) and the hypoxia-inducible factor-1. Biol Chem 378:609–616.PubMedGoogle Scholar
  239. Wilk, R., Weizman, I., Shilo, B.Z. (1996). Trachealess encodes a bHLH-PAS protein that is an inducer of tracheal cell fates in Drosophila. Genes Dev 10:93–102.PubMedGoogle Scholar
  240. Wilt, F.H. (1964). Erythropoesis in the chick embryo: the role of endoderm. Science 147: 1588–1590.Google Scholar
  241. Wilting, J., Brand-Saberi, B., Huang, R., et al. (1995). Angiogenic potential of the avian somite. Dev Dyn 202:165–171.PubMedGoogle Scholar
  242. Wilting, J., Christ, B., Weich, H.A. (1992). The effects of growth factors on the day 13 chorioallantoic membrane (CAM): a study of VEGF165 and PDGF-BB. Anat Embryol Berl 186:251–257.PubMedGoogle Scholar
  243. Wizigmann-Voos, S., Breier, G., Risau, W., Plate, K.H. (1995). Up-regulation of vascular endothelial growth factor and its receptors in von Hippel-Lindau disease-associated and sporadic hemangioblastomas. Cancer Res 55:1358–1364.PubMedGoogle Scholar
  244. Yamaguchi, T.P., Dumont, D.J., Conlon, R.A., Breitman, M.L., Rossant, J. (1993). flk-1, an fit-related receptor tyrosine kinase is an early marker for endothelial cell precursors. Development 118:489–498.PubMedGoogle Scholar
  245. Yancopoulos, G., Klagsbrun, M., Folkman, J. (1998). Vasculogenesis, angiogenesis, and growth factors: ephrins enter the fray at the border. Cell 29:661–664.Google Scholar
  246. Yang, X.J., Cepko, C.L. (1996). Flk-1, a receptor for vascular endothelial growth factor (VEGF), is expressed by retinal progenitor cells. J Neurosci 16:6089–6099.PubMedGoogle Scholar
  247. Yano, M., Iwama, A., Nishio, H., Suda, J., Takada, G., Suda, T. (1997). Expression and function of murine receptor tyrosine kinases, TIE and TEK, in hematopoietic stem cells. Blood 89:4317–4326.PubMedGoogle Scholar
  248. Yoshida, A., Anand-Apte, B., Zetter, B.R. (1996). Differential endothelial migration and proliferation to basic fibroblast growth factor and vascular endothelial growth factor. Growth Factors 13:57–64.PubMedGoogle Scholar
  249. Zagris, N. (1980). Erythroid cell differentiation in unincubated chick blastoderm in culture. J Embryol Exp Morphol 58:209–216.PubMedGoogle Scholar
  250. Zelzer, E., Wappner, P., Shilo, B.Z. (1997). The PAS domain confers target gene specificity of Drosophila bHLH/PAS proteins. Genes Dev 11:2079–2089.PubMedGoogle Scholar
  251. Ziegler, B.L., Valtieri, M., Porada, G.A., et al. (1999). KDR receptor: a key marker defining hematopoietic stem cells. Science 285:1553–1558.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2002

Authors and Affiliations

  • Ingo Flamme
  • Georg Breier

There are no affiliations available

Personalised recommendations