Flt4

Summary

Gene Symbol: Flt4
Description: FMS-like tyrosine kinase 4
Alias: AI323512, Chy, Flt-4, VEGFR-3, VEGFR3, vascular endothelial growth factor receptor 3, chylous ascites, receptor protein tyrosine kinase, tyrosine-protein kinase receptor FLT4
Species: mouse

Top Publications

  1. ncbi Vascular endothelial growth factor receptor-3 in hypoxia-induced vascular development
    Ingrid Nilsson
    Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden
    FASEB J 18:1507-15. 2004
  2. pmc Spreds are essential for embryonic lymphangiogenesis by regulating vascular endothelial growth factor receptor 3 signaling
    Koji Taniguchi
    Division of Molecular and Cellular Immunology, Medical Institute of Bioregulation, Kyushu University, 3 1 1 Maidashi, Fukuoka, Japan
    Mol Cell Biol 27:4541-50. 2007
  3. doi VEGFR-3/Flt-4 mediates proliferation and chemotaxis in glial precursor cells
    Sandra Kranich
    Department of Anatomy, University of Kiel, Olshausenstrasse 40, 24098 Kiel, Germany
    Neurochem Int 55:747-53. 2009
  4. doi Suppression of lymphangiogenesis induced by Flt-4 antibody in gastric low-grade mucosa-associated lymphoid tissue lymphoma by Helicobacter heilmannii infection
    Masahiko Nakamura
    Division of Pathophysiolgy, Research and Education Center for Clinical Pharmacy, School of Pharmaceutical Sciences, Mitaka, Tokyo, Japan
    J Gastroenterol Hepatol 25:S1-6. 2010
  5. pmc ALK5 phosphorylation of the endoglin cytoplasmic domain regulates Smad1/5/8 signaling and endothelial cell migration
    Bridgette N Ray
    Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27708, USA
    Carcinogenesis 31:435-41. 2010
  6. ncbi Failure of blood-island formation and vasculogenesis in Flk-1-deficient mice
    F Shalaby
    Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada
    Nature 376:62-6. 1995
  7. ncbi Role of the Flt-1 receptor tyrosine kinase in regulating the assembly of vascular endothelium
    G H Fong
    Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada
    Nature 376:66-70. 1995
  8. pmc Expression of the fms-like tyrosine kinase 4 gene becomes restricted to lymphatic endothelium during development
    A Kaipainen
    Molecular Cancer Biology Laboratory, University of Helsinki, Finland
    Proc Natl Acad Sci U S A 92:3566-70. 1995
  9. ncbi VEGF-C receptor binding and pattern of expression with VEGFR-3 suggests a role in lymphatic vascular development
    E Kukk
    Molecular Cancer Biology Laboratory, Haartman Institute, University of Helsinki, Finland
    Development 122:3829-37. 1996
  10. ncbi Cardiovascular failure in mouse embryos deficient in VEGF receptor-3
    D J Dumont
    Ontario Cancer Institute and Amgen Institute, Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada M5G 2C1
    Science 282:946-9. 1998

Scientific Experts

Detail Information

Publications121 found, 100 shown here

  1. ncbi Vascular endothelial growth factor receptor-3 in hypoxia-induced vascular development
    Ingrid Nilsson
    Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden
    FASEB J 18:1507-15. 2004
    ..In addition, sequestering of VEGF receptor-3 ligands reduced vascularization in a manner similar to neutralization of VEGF receptor-3. We conclude that hypoxia-driven vascular development requires the activity of VEGF receptor-3...
  2. pmc Spreds are essential for embryonic lymphangiogenesis by regulating vascular endothelial growth factor receptor 3 signaling
    Koji Taniguchi
    Division of Molecular and Cellular Immunology, Medical Institute of Bioregulation, Kyushu University, 3 1 1 Maidashi, Fukuoka, Japan
    Mol Cell Biol 27:4541-50. 2007
    ..These data suggest that Spreds play an important role in lymphatic vessel development by negatively regulating VEGF-C/VEGFR-3 signaling...
  3. doi VEGFR-3/Flt-4 mediates proliferation and chemotaxis in glial precursor cells
    Sandra Kranich
    Department of Anatomy, University of Kiel, Olshausenstrasse 40, 24098 Kiel, Germany
    Neurochem Int 55:747-53. 2009
    ..These results show that VEGF-C/-D together with its receptor VEGFR-3 provides an auto-/paracrine growth and chemotactic system for glial precursors in the developing brain...
  4. doi Suppression of lymphangiogenesis induced by Flt-4 antibody in gastric low-grade mucosa-associated lymphoid tissue lymphoma by Helicobacter heilmannii infection
    Masahiko Nakamura
    Division of Pathophysiolgy, Research and Education Center for Clinical Pharmacy, School of Pharmaceutical Sciences, Mitaka, Tokyo, Japan
    J Gastroenterol Hepatol 25:S1-6. 2010
    ..The present study was undertaken to elucidate the interaction of this tumor with angiogenesis and lymphangiogenesis. In addition, the effect of Flt-4 antibodies on lymphoma expansion was investigated...
  5. pmc ALK5 phosphorylation of the endoglin cytoplasmic domain regulates Smad1/5/8 signaling and endothelial cell migration
    Bridgette N Ray
    Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27708, USA
    Carcinogenesis 31:435-41. 2010
    ..Taken together, these results support endoglin phosphorylation by ALK5 as an important mechanism for regulating TGF-beta superfamily signaling and migration in endothelial cells...
  6. ncbi Failure of blood-island formation and vasculogenesis in Flk-1-deficient mice
    F Shalaby
    Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada
    Nature 376:62-6. 1995
    ..These results indicate that Flk-1 is essential for yolk-sac blood-island formation and vasculogenesis in the mouse embryo...
  7. ncbi Role of the Flt-1 receptor tyrosine kinase in regulating the assembly of vascular endothelium
    G H Fong
    Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada
    Nature 376:66-70. 1995
    ..We suggest that the Flt-1 signalling pathway may regulate normal endothelial cell-cell or cell-matrix interactions during vascular development...
  8. pmc Expression of the fms-like tyrosine kinase 4 gene becomes restricted to lymphatic endothelium during development
    A Kaipainen
    Molecular Cancer Biology Laboratory, University of Helsinki, Finland
    Proc Natl Acad Sci U S A 92:3566-70. 1995
    We have recently cloned the human fms-like tyrosine kinase 4 gene FLT4, whose protein product is related to two vascular endothelial growth factor receptors FLT1 and KDR/FLK1...
  9. ncbi VEGF-C receptor binding and pattern of expression with VEGFR-3 suggests a role in lymphatic vascular development
    E Kukk
    Molecular Cancer Biology Laboratory, Haartman Institute, University of Helsinki, Finland
    Development 122:3829-37. 1996
    ..The recombinant mouse VEGF-C protein was secreted from transfected cells as VEGFR-3 (Flt4) binding polypeptides of 30-32x10(3) Mr and 22-23x10(3) Mr which preferentially stimulated the autophosphorylation ..
  10. ncbi Cardiovascular failure in mouse embryos deficient in VEGF receptor-3
    D J Dumont
    Ontario Cancer Institute and Amgen Institute, Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada M5G 2C1
    Science 282:946-9. 1998
    ..5. Thus, VEGFR-3 has an essential role in the development of the embryonic cardiovascular system before the emergence of the lymphatic vessels...
  11. ncbi Prox1 function is required for the development of the murine lymphatic system
    J T Wigle
    Department of Genetics, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    Cell 98:769-78. 1999
    ..These findings suggest that Prox1 is a specific and required regulator of the development of the lymphatic system and that the vascular and lymphatic systems develop independently...
  12. pmc Signalling via vascular endothelial growth factor receptor-3 is sufficient for lymphangiogenesis in transgenic mice
    T Veikkola
    Molecular Cancer Biology Laboratory and Ludwig Institute for Cancer Research, Haartman Institute, University of Helsinki, PO Box 21 Haartmaninkatu 3, 00014 Helsinki, Finland
    EMBO J 20:1223-31. 2001
    ..Evidence was also obtained that these growth factors act in a paracrine manner in vivo. These results demonstrate that stimulation of the VEGFR-3 signal transduction pathway is sufficient to induce specifically lymphangiogenesis in vivo...
  13. ncbi The specificity of receptor binding by vascular endothelial growth factor-d is different in mouse and man
    M E Baldwin
    Ludwig Institute for Cancer Research, Post Office Box 2008, Royal Melbourne Hospital, Victoria 3050 Australia
    J Biol Chem 276:19166-71. 2001
    ..This suggests that VEGF-D and VEGFR-3 may play a role in establishing vessels of the skin by a paracrine mechanism. Our study of receptor specificity suggests that VEGF-D may have different biological functions in mouse and man...
  14. pmc A model for gene therapy of human hereditary lymphedema
    M J Karkkainen
    Molecular Cancer Biology Laboratory and Ludwig Institute for Cancer Research, Haartman Institute and Helsinki University Hospital, Biomedicum Helsinki, University of Helsinki, P O B 63 Haartmaninkatu 8, 00014 Helsinki, Finland
    Proc Natl Acad Sci U S A 98:12677-82. 2001
    ..Like the human patients, the lymphedema (Chy) mice have an inactivating Vegfr3 mutation in their germ line, and swelling of the limbs because of hypoplastic cutaneous, but not visceral, ..
  15. pmc An essential role for Prox1 in the induction of the lymphatic endothelial cell phenotype
    Jeffrey T Wigle
    Department of Genetics, St Jude Children s Research Hospital, Memphis, TN 38105, USA
    EMBO J 21:1505-13. 2002
    ..On the basis of our findings, we propose that a blood vascular phenotype is the default fate of budding embryonic venous endothelial cells; upon expression of Prox1, these budding cells adopt a lymphatic vasculature phenotype...
  16. pmc Blockade of vascular endothelial growth factor receptor-3 signaling inhibits fibroblast growth factor-2-induced lymphangiogenesis in mouse cornea
    Hajime Kubo
    Molecular Cancer Biology Laboratory and Ludwig Institute for Cancer Research, and Helsinki University Central Hospital, Biomedicum Helsinki, University of Helsinki, POB 63, Haartmaninkatu 8, 00014, Helsinki, Finland
    Proc Natl Acad Sci U S A 99:8868-73. 2002
    ..Because increased expression of FGF-2 and VEGF-C has been associated with lymphatic metastasis, our results provide a potential strategy for the inhibition of lymphatic metastasis in cancer therapy...
  17. ncbi Abnormal lymphatic vessel development in neuropilin 2 mutant mice
    Li Yuan
    INSERM U36, College de France, 11, place Marcelin Berthelot, 75005 Paris, France
    Development 129:4797-806. 2002
    ..Arteries, veins and larger, collecting lymphatic vessels developed normally, suggesting that neuropilin 2 is selectively required for the formation of small lymphatic vessels and capillaries...
  18. ncbi Modulation of VEGFR-2-mediated endothelial-cell activity by VEGF-C/VEGFR-3
    Kazuyoshi Matsumura
    Division of Gastroenterology and Hepatology, Department of Internal Medicine, Graduate School of Medicine, Kyoto University, Japan
    Blood 101:1367-74. 2003
    ..Moreover, our findings suggest that the mechanisms underlying AFL4-induced EC dispersion are distinct from those underlying VECD-1-induced dispersion for maintenance of EC integrity...
  19. pmc Novel expression of vascular endothelial growth factor receptor (VEGFR)-3 and VEGF-C on corneal dendritic cells
    Pedram Hamrah
    Laboratory of Immunology, Schepens Eye Research Institute and the Massachusetts Eye and Ear Infirmary and Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, USA
    Am J Pathol 163:57-68. 2003
    ..These data demonstrate, for the first time, the expression of VEGFR-3 and VEGF-C on tissue DC, which implicate a novel potential relationship between lymphangiogenesis and leukocyte trafficking in the eye...
  20. ncbi Vascular endothelial growth factor C is required for sprouting of the first lymphatic vessels from embryonic veins
    Marika J Karkkainen
    Molecular Cancer Biology Laboratory and Ludwig Institute for Cancer Research, Haartman Institute and Helsinki University Hospital, Biomedicum Helsinki, University of Helsinki, PO Box 63, 00014 Helsinki, Finland
    Nat Immunol 5:74-80. 2004
    ..Our results indicate that VEGF-C is the paracrine factor essential for lymphangiogenesis, and show that both Vegfc alleles are required for normal lymphatic development...
  21. ncbi Complete and specific inhibition of adult lymphatic regeneration by a novel VEGFR-3 neutralizing antibody
    Bronislaw Pytowski
    Molecular and Cellular Biology, ImClone Systems, New York, NY, USA
    J Natl Cancer Inst 97:14-21. 2005
    New lymphatic growth may contribute to tumor metastasis. Activation of vascular endothelial growth factor receptor 3 (VEGFR-3) by its ligands VEGF-C and -D is necessary for embryonic and tumor lymphangiogenesis...
  22. pmc PDZ interaction site in ephrinB2 is required for the remodeling of lymphatic vasculature
    Taija Makinen
    Department of Molecular Neurobiology, Max Planck Institute of Neurobiology, 82152 Munich Martinsried, Germany
    Genes Dev 19:397-410. 2005
    ..Our studies define ephrinB2 as an essential regulator of lymphatic development and indicate that interactions with PDZ domain effectors are required to mediate its functions...
  23. ncbi Angiopoietin-1 promotes lymphatic sprouting and hyperplasia
    Tuomas Tammela
    Molecular Cancer Biology Laboratory, Ludwig Institute for Cancer Research, Biomedicum Helsinki, Finland
    Blood 105:4642-8. 2005
    ..lymphatic endothelial cells and Ang1 stimulation of these cells resulted in up-regulation of vascular endothelial growth factor receptor 3 (VEGFR-3). Furthermore, a soluble form of VEGFR-3 inhibited the observed lymphatic sprouting...
  24. pmc Lymphangiogenic growth factor responsiveness is modulated by postnatal lymphatic vessel maturation
    Terhi Karpanen
    Molecular Cancer Biology Laboratory, Biomedicum Helsinki, P O B 63 Haartmaninkatu 8, FI 00014 University of Helsinki, Finland
    Am J Pathol 169:708-18. 2006
    ..These results indicate considerable plasticity of lymphatic vessels during the early postnatal period but not thereafter, suggesting that anti-lymphangiogenic therapy can be safely applied in adults...
  25. ncbi Cooperative and redundant roles of VEGFR-2 and VEGFR-3 signaling in adult lymphangiogenesis
    Jeremy Goldman
    Institute of Bioengineering, School of Life Sciences, Ecole Polytechnique Federale de Lausanne, 1015 Lausanne, Switzerland
    FASEB J 21:1003-12. 2007
    ..Our findings demonstrate that cooperative signaling of VEGFR-2 and -3 is necessary for lymphatic migration and proliferation, but VEGFR-3 is redundant with VEGFR-2 for LEC organization into functional capillaries...
  26. pmc Prox1 induces lymphatic endothelial differentiation via integrin alpha9 and other signaling cascades
    Koichi Mishima
    Department of Molecular Pathology, Graduate School of Medicine, University of Tokyo, Tokyo 113 0033, Japan
    Mol Biol Cell 18:1421-9. 2007
    ..preferentially migrated toward VEGF-C via up-regulation of the expression of integrin alpha9 and VEGF receptor 3 (VEGFR3)...
  27. ncbi A Gata2 intronic enhancer confers its pan-endothelia-specific regulation
    Melin Khandekar
    Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109 2200, USA
    Development 134:1703-12. 2007
    ..Thus, GATA-2 is expressed early in lymphatic, cardiac and blood vascular endothelial cells, and the pan-endothelium-specific expression of Gata2 is controlled by a discrete intronic enhancer...
  28. pmc Distinct vascular endothelial growth factor signals for lymphatic vessel enlargement and sprouting
    Maria Wirzenius
    Molecular Cancer Biology Laboratory and Ludwig Institute for Cancer Research, Haartman Institute and Helsinki University Hospital, Biomedicum Helsinki, University of Helsinki, 00014 Helsinki, Finland
    J Exp Med 204:1431-40. 2007
    ..Our data suggests that VEGFR-2 signals promote lymphatic vessel enlargement, but unlike in the blood vessels, are not involved in vessel sprouting to generate new lymphatic vessels in vivo...
  29. ncbi Lymphatic development in mouse small intestine
    Kyung Eun Kim
    National Research Laboratory of Vascular Biology and Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Korea
    Dev Dyn 236:2020-5. 2007
    ..development by immunostaining with recently discovered molecular markers for lymphatic endothelial cells: LYVE-1, VEGFR3, Prox-1, and podoplanin...
  30. doi Expression of the hyaluronan receptor LYVE-1 is not restricted to the lymphatic vasculature; LYVE-1 is also expressed on embryonic blood vessels
    Emma J Gordon
    Division of Haematology, The Hanson Institute, Adelaide, South Australia, Australia
    Dev Dyn 237:1901-9. 2008
    ..Our data are also the first demonstration, to our knowledge, that the mouse yolk sac is devoid of lymphatic vessels...
  31. doi Blocking VEGFR-3 suppresses angiogenic sprouting and vascular network formation
    Tuomas Tammela
    Molecular Cancer Biology Laboratory and Ludwig Institute for Cancer Research, Biomedicum Helsinki and the Haartman Institute University of Helsinki, PO Box 63 Haartmaninkatu 8, 00014 Helsinki, Finland
    Nature 454:656-60. 2008
    ..Our results implicate VEGFR-3 as a regulator of vascular network formation. Targeting VEGFR-3 may provide additional efficacy for anti-angiogenic therapies, especially towards vessels that are resistant to VEGF or VEGFR-2 inhibitors...
  32. pmc NFATc1 regulates lymphatic endothelial development
    Rishikesh M Kulkarni
    Division of Pulmonary Biology, MLC7009, Cincinnati Children s Hospital Research Foundation, Cincinnati, OH 45229, USA
    Mech Dev 126:350-65. 2009
    ..In reporter assays, NFATc1 activated lymphatic specific gene promoters. These results demonstrate the role of calcineurin-NFAT pathway in lymphangiogenesis and suggest that NFATc1 is the principle NFAT involved...
  33. pmc FOXC2 controls formation and maturation of lymphatic collecting vessels through cooperation with NFATc1
    Camilla Norrmen
    Molecular Cancer Biology Program, Biomedicum Helsinki, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland
    J Cell Biol 185:439-57. 2009
    ..As damage to collecting vessels is a major cause of lymphatic dysfunction in humans, our results suggest that FOXC2 and NFATc1 are potential targets for therapeutic intervention...
  34. pmc Integrin-alpha9 is required for fibronectin matrix assembly during lymphatic valve morphogenesis
    Eleni Bazigou
    Lymphatic Development Laboratory, Cancer Research UK London Research Institute, 44 Lincoln s Inn Fields, London WC2A 3PX, UK
    Dev Cell 17:175-86. 2009
    ..Our findings reveal an important role for integrin-alpha9 signaling during lymphatic valve morphogenesis and implicate it as a candidate gene for primary lymphedema caused by valve defects...
  35. pmc Inhibition of lymphangiogenesis and lymphatic drainage via vascular endothelial growth factor receptor 3 blockade increases the severity of inflammation in a mouse model of chronic inflammatory arthritis
    Ruolin Guo
    Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA
    Arthritis Rheum 60:2666-76. 2009
    ..This study was undertaken to investigate the effect of lymphatic inhibition on joint and draining lymph node (LN) pathology during the course of arthritis progression in mice...
  36. pmc Neuropilin-2 mediates VEGF-C-induced lymphatic sprouting together with VEGFR3
    Yunling Xu
    Institut National de la Sante et de la Recherche Medicale, Unité 833, 75005 Paris, France
    J Cell Biol 188:115-30. 2010
    ..Thus, interaction between Nrp2 and VEGFR3 mediates proper lymphatic vessel sprouting in response to VEGF-C.
  37. doi Novel function for blood platelets and podoplanin in developmental separation of blood and lymphatic circulation
    Pavel Uhrin
    Department of Vascular Biology and Thrombosis Research, Center for Biomolecular Medicine and Pharmacology, Medical University of Vienna, Vienna, Austria
    Blood 115:3997-4005. 2010
    ..Therefore, interaction of endothelial podoplanin of the developing lymph sac with circulating platelets from the cardinal vein is critical for separating the lymphatic from the blood vascular system...
  38. doi H-, N- and Kras cooperatively regulate lymphatic vessel growth by modulating VEGFR3 expression in lymphatic endothelial cells in mice
    Taeko Ichise
    Laboratory of Developmental Genetics, Center for Experimental Medicine and Systems Biology, Institute of Medical Science, University of Tokyo, Minato ku, Tokyo 108 8639, Japan
    Development 137:1003-13. 2010
    ..The close link between Ras and VEGFR3 in vitro is consistent with the result that Ras knockout and transgenic alleles are genetic modifiers in lymphatic ..
  39. doi VEGFR-3 ligand-binding and kinase activity are required for lymphangiogenesis but not for angiogenesis
    Luqing Zhang
    Laboratory of Vascular and Cancer Biology, MOE Key Laboratory for Model Animal and Disease Study, Model Animal Research Institute, Nanjing University, 12 Xue Fu Road, Nanjing 210061, China
    Cell Res 20:1319-31. 2010
    ..two genetically modified mouse models in this study, targeting the coding region for the ligand-binding domain (Vegfr3(ΔLBD)) or the tyrosine kinase domain with an inactivation point mutation (Vegfr3(TKmut))...
  40. doi Lymphatic ontogeny and effect of hypoplasia in developing lung
    Rishikesh M Kulkarni
    Division of Pulmonary Biology, Cincinnati Children s Hospital Research Foundation, Cincinnati, OH 45229, USA
    Mech Dev 128:29-40. 2011
    ..Surfactant synthesis was unaffected. Together, these data demonstrate that lung lymphatics develop autonomously and that pulmonary lymphatic hypoplasia is detrimental to survival of the neonate due to impaired lung fluid clearance...
  41. doi CCBE1 is essential for mammalian lymphatic vascular development and enhances the lymphangiogenic effect of vascular endothelial growth factor-C in vivo
    Frank L Bos
    Hubrecht Institute KNAW, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands
    Circ Res 109:486-91. 2011
    ..Insight into the molecular role of CCBE1 is completely lacking, and mouse models for the disease do not exist...
  42. pmc Prox1 dosage controls the number of lymphatic endothelial cell progenitors and the formation of the lymphovenous valves
    R Sathish Srinivasan
    Department of Genetics, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    Genes Dev 25:2187-97. 2011
    ..This is the first report describing the molecular mechanism controlling lymphovenous communication...
  43. pmc Mechanoinduction of lymph vessel expansion
    Lara Planas-Paz
    Institute of Metabolic Physiology, Heinrich Heine University, Dusseldorf, Germany
    EMBO J 31:788-804. 2012
    ..reduces the length of LECs, decreases tyrosine phosphorylation of vascular endothelial growth factor receptor-3 (VEGFR3), and inhibits LEC proliferation...
  44. doi Mechanotransduction, PROX1, and FOXC2 cooperate to control connexin37 and calcineurin during lymphatic-valve formation
    Amélie Sabine
    Division of Experimental Oncology, Multidisciplinary Oncology Center, University Hospital of Lausanne, Switzerland
    Dev Cell 22:430-45. 2012
    ..Our results also provide molecular insights into the role of endothelial cell identity in the regulation of vascular mechanotransduction...
  45. ncbi Defective valves and abnormal mural cell recruitment underlie lymphatic vascular failure in lymphedema distichiasis
    Tatiana V Petrova
    Molecular Cancer Biology Laboratory and Ludwig Institute for Cancer Research, Biomedicum Helsinki and Helsinki University Central Hospital, University of Helsinki, Haartmaninkatu 8, P O B 63, 00014 Helsinki, Finland
    Nat Med 10:974-81. 2004
    ..individuals with LD and in mice heterozygous for Foxc2 and for the gene encoding lymphatic endothelial receptor, Vegfr3 (also known as Flt4)...
  46. pmc Deletion of vascular endothelial growth factor C (VEGF-C) and VEGF-D is not equivalent to VEGF receptor 3 deletion in mouse embryos
    Paula Haiko
    Molecular Cancer Biology Laboratory, Haartman Institute, Biomedicum Helsinki and Helsinki University Central Hospital, P O B 63 Haartmaninkatu 8, University of Helsinki, 00014 Helsinki, Finland
    Mol Cell Biol 28:4843-50. 2008
    ..We analyzed mice deficient in both of the known VEGFR-3 ligands, VEGF-C and VEGF-D. Unlike the Vegfr3(-/-) embryos, the Vegfc(-/-); Vegfd(-/-) embryos displayed normal blood vasculature after embryonic day 9.5...
  47. ncbi Foxc2 is expressed in developing lymphatic vessels and other tissues associated with lymphedema-distichiasis syndrome
    Susan L Dagenais
    Department of Human Genetics, University of Michigan, 4909 Buhl, Box 0618, 1241 E Catherine Street, Ann Arbor, MI 48109 0618, USA
    Gene Expr Patterns 4:611-9. 2004
    ....
  48. pmc Abnormal embryonic lymphatic vessel development in Tie1 hypomorphic mice
    Xianghu Qu
    Division of Pediatric Cardiology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
    Development 137:1285-95. 2010
    ..No defects were observed in the arterial or venous vasculature. These results suggest that the developing lymphatic vasculature is particularly sensitive to alterations in Tie1 expression...
  49. pmc Embryonic vascular endothelial cells are malleable to reprogramming via Prox1 to a lymphatic gene signature
    Harold Kim
    Sunnybrook Research Institute University of Toronto 2075 Bayview Avenue Toronto, Ontario M4N 3M5, Canada
    BMC Dev Biol 10:72. 2010
    ..While the in vitro data suggest that gene reprogramming occurs upon Prox1 expression, it is not clear if this is a direct result of Prox1 in vascular endothelial cells in vivo...
  50. pmc Genes regulating lymphangiogenesis control venous valve formation and maintenance in mice
    Eleni Bazigou
    Lymphatic Development Laboratory, Cancer Research UK London Research Institute, London, UK
    J Clin Invest 121:2984-92. 2011
    ..and mature venous valves also expressed a repertoire of proteins, including prospero-related homeobox 1 (Prox1), Vegfr3, and integrin-α9, previously characterized as specific and critical regulators of lymphangiogenesis...
  51. pmc Blocking Fibroblast Growth Factor receptor signaling inhibits tumor growth, lymphangiogenesis, and metastasis
    Frederic Larrieu-Lahargue
    Laboratoire de l Angiogenèse et du Microenvironement des Cancers, Universite de Bordeaux, Talence, France
    PLoS ONE 7:e39540. 2012
    ....
  52. pmc Vascular endothelial growth factor receptor-2 promotes the development of the lymphatic vasculature
    Michael T Dellinger
    Division of Surgical Oncology, Department of Surgery, Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America
    PLoS ONE 8:e74686. 2013
    ..Together, this work demonstrates that VEGFR2 directly promotes the expansion of the lymphatic network and further defines the molecular mechanisms controlling the development of the lymphatic vascular system. ..
  53. pmc Molecular identification of venous progenitors in the dorsal aorta reveals an aortic origin for the cardinal vein in mammals
    Henrik Lindskog
    Laboratory for Accelerated Vascular Research, Division of Vascular Surgery, Department of Surgery, University of California, San Francisco, CA 94143, USA
    Development 141:1120-8. 2014
    ..Therefore, our cellular and molecular evidence suggests that the DA harbors venous progenitors that move to participate in CV formation, and that ephrin B2/EphB4 signaling regulates this aortic contribution to the mammalian CV. ..
  54. pmc VEGFR3 does not sustain retinal angiogenesis without VEGFR2
    Georgia Zarkada
    Wihuri Research Institute and Translational Cancer Biology Program, Biomedicum Helsinki, University of Helsinki, FIN 00014 Helsinki, Finland
    Proc Natl Acad Sci U S A 112:761-6. 2015
    ..b>VEGFR3 is expressed in all endothelia and is indispensable for angiogenesis during early embryonic development...
  55. pmc The matricellular protein CCN1 controls retinal angiogenesis by targeting VEGF, Src homology 2 domain phosphatase-1 and Notch signaling
    Hemabindu Chintala
    State University of New York SUNY Eye Institute and Department of Cell Biology, Downstate Medical Center, Brooklyn, NY 11203, USA
    Development 142:2364-74. 2015
    ..These data highlight novel functions of CCN1 as a naturally optimized molecule, fine-controlling key processes in physiological angiogenesis and safeguarding against aberrant angiogenic responses. ..
  56. pmc Defective lymphatic valve development and chylothorax in mice with a lymphatic-specific deletion of Connexin43
    Stephanie J Munger
    Department of Physiology, University of Arizona, Tucson AZ 85724, USA Electronic address
    Dev Biol 421:204-218. 2017
    ..These results demonstrate that the expression of Cx43 is specifically required in LECs for normal development of LVs...
  57. ncbi Involvement of insulin-like growth factor 2 in angiogenic factor transcription in Bi-maternal mouse conceptuses
    Manabu Kawahara
    Laboratory of Animal Resource Development, Faculty of Agriculture, Saga University, Japan
    J Reprod Dev 56:79-85. 2010
    ..clarify this, we performed quantitative gene expression analysis for representative angiogenic factors-Vegf, Flt1, Flt4, Flk1, Ang1, Ang2, Tie1, and Tie2-for 3 types of bi-maternal conceptuses containing genomes with non-growing (ng) ..
  58. pmc ALK1 signaling regulates early postnatal lymphatic vessel development
    Kyle Niessen
    Department of Tumor Biology and Angiogenesis, Division of Research, Genentech Inc, 1 DNA Way, South San Francisco, CA 94080, USA
    Blood 115:1654-61. 2010
    ..simultaneous inhibition of ALK1 pathway increases apoptosis in lymphatic vessels caused by blockade of VEGFR3 signaling...
  59. pmc Impaired angiogenesis and altered Notch signaling in mice overexpressing endothelial Egfl7
    Donna Nichol
    Department of Cell and Developmental Biology, Weill Cornell Medical College, New York, NY 10065, USA
    Blood 116:6133-43. 2010
    ..In conclusion, we have uncovered a critical role for Egfl7 in vascular development and have shown that some of these functions are mediated through modulation of Notch signaling...
  60. pmc Combined blockade of VEGFR-2 and VEGFR-3 inhibits inflammatory lymphangiogenesis in early and middle stages
    Don Yuen
    Center of Eye Disease and Development, Program in Vision Science, and School of Optometry, University of California, Berkeley, CA 94720, USA
    Invest Ophthalmol Vis Sci 52:2593-7. 2011
    ..The purpose of this study was to investigate whether there is a time window for therapeutic intervention of corneal LG and whether a combined blockade of VEGFR-2 and VEGFR-3 effectively suppresses early-, middle-, or late-stage LG...
  61. pmc Mirtron microRNA-1236 inhibits VEGFR-3 signaling during inflammatory lymphangiogenesis
    Dennis Jones
    Interdepartmental Program in Vascular Biology and Therapeutics, Department of Immunobiology, Yale University School of Medicine, 10 Amistad St, New Haven, CT 06520, USA
    Arterioscler Thromb Vasc Biol 32:633-42. 2012
    ..The goal of this study was to investigate how VEGFR-3 expression is regulated during inflammatory lymphangiogenesis...
  62. doi Notch-dependent VEGFR3 upregulation allows angiogenesis without VEGF-VEGFR2 signalling
    Rui Benedito
    Max Planck Institute for Molecular Biomedicine, Department of Tissue Morphogenesis, D 48149 Munster, Germany
    Nature 484:110-4. 2012
    ..By contrast, VEGFR3, the main receptor for VEGF-C, was strongly modulated by Notch...
  63. pmc In vivo imaging of lymphatic vessels in development, wound healing, inflammation, and tumor metastasis
    Inés Martínez-Corral
    Biotechnology Programme, Spanish National Cancer Research Centre, CNIO, 28029 Madrid, Spain
    Proc Natl Acad Sci U S A 109:6223-8. 2012
    ..Here, we present the Vegfr3(EGFPLuc) mouse model, where an EGFP-luciferase fusion protein, expressed under the endogenous transcriptional ..
  64. pmc Target gene analysis by microarrays and chromatin immunoprecipitation identifies HEY proteins as highly redundant bHLH repressors
    Julia Heisig
    Developmental Biochemistry, Theodor Boveri Institute, Biocenter, University of Wuerzburg, Wuerzburg, Germany
    PLoS Genet 8:e1002728. 2012
    ..These data clearly establish the three HEY bHLH factors as highly redundant transcriptional repressors in vitro and in vivo, which explains the combinatorial action observed in different tissues with overlapping expression...
  65. pmc Characterization and therapeutic potential of induced pluripotent stem cell-derived cardiovascular progenitor cells
    Ali Nsair
    Department of Medicine and Physiology, Cardiovascular Research Laboratory, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America
    PLoS ONE 7:e45603. 2012
    ..Study of endogenous and induced pluripotent stem cell (iPSC)-derived CPCs has been limited due to the lack of specific cell surface markers to isolate them and conditions for their in vitro expansion that maintain their multipotency...
  66. pmc Soluble vascular endothelial growth factor receptor 3 is essential for corneal alymphaticity
    Nirbhai Singh
    Moran Eye Center, University of Utah, 65 Mario Capecchi Drive, Salt Lake City, UT 84132, USA
    Blood 121:4242-9. 2013
    ..Membrane-bound vascular endothelial growth factor receptor 3 (VEGFR-3), with its cognate ligand vascular endothelial growth factor C (VEGF-C), is a major ..
  67. ncbi Chromosomal localization of FLT4, a novel receptor-type tyrosine kinase gene
    F Galland
    Laboratory of Molecular Oncology, U 119 INSERM, Marseille, France
    Genomics 13:475-8. 1992
    ..The gene was named FLT4. Cosmid clones of the mouse Flt4 gene were isolated...
  68. ncbi Characterization of murine Flt4 ligand/VEGF-C
    L J Fitz
    Genetics Institute, Inc, Cambridge, Massachusetts 02140, USA
    Oncogene 15:613-8. 1997
    Flt4 is a receptor protein tyrosine kinase that is expressed in the adult lymphatic endothelium and high endothelial venules...
  69. ncbi The transcription factor MEF2C-null mouse exhibits complex vascular malformations and reduced cardiac expression of angiopoietin 1 and VEGF
    W Bi
    Division of Cardiology, University of Texas Medical School at Houston, Houston, Texas, 77030, USA
    Dev Biol 211:255-67. 1999
    ....
  70. ncbi VEGF-C signaling pathways through VEGFR-2 and VEGFR-3 in vasculoangiogenesis and hematopoiesis
    K Hamada
    Department of Cell Differentiation, Institute of Molecular Embryology and Genetics, Kumamoto University, Japan
    Blood 96:3793-800. 2000
    ..This indicates that elaborated control through VEGFR-3 signaling is critical in vasculoangiogenesis and hematopoiesis. (Blood. 2000;96:3793-3800)..
  71. pmc Erk5 null mice display multiple extraembryonic vascular and embryonic cardiovascular defects
    Christopher P Regan
    Vertex Pharmaceuticals, Department of Biology, 130 Waverly Street, Cambridge, MA 02139, USA
    Proc Natl Acad Sci U S A 99:9248-53. 2002
    ..Together, these data define an essential role for Erk5 in cardiovascular development. Moreover, the inability of Erk5-deficient mice to form a complex vasculature suggests that Erk5 may play an important role in controlling angiogenesis...
  72. ncbi Expression of vascular endothelial growth factor receptor-3 (VEGFR-3) in the conjunctiva--a potential link between lymphangiogenesis and leukocyte trafficking on the ocular surface
    Pedram Hamrah
    Laboratory of Immunology, Schepens Eye Research Institute and the Department of Ophthalmology Harvard Medical School Boston, Massachusetts, USA
    Adv Exp Med Biol 506:851-60. 2002
  73. ncbi Angiopoietin-1 promotes LYVE-1-positive lymphatic vessel formation
    Tohru Morisada
    Department of Cell Differentiation, The Sakaguchi Laboratory, School of Medicine, Keio University, Tokyo, Japan
    Blood 105:4649-56. 2005
    ..On the basis of these observations, we propose that Ang signaling regulates lymphatic vessel formation through Tie2...
  74. ncbi VEGF-C is a trophic factor for neural progenitors in the vertebrate embryonic brain
    Barbara Le Bras
    Institut National de la Sante et de la Recherche Medicale INSERM, U711, Paris F 75013, France
    Nat Neurosci 9:340-8. 2006
    ..VEGF-C thus has a new, evolutionary conserved function as a growth factor selectively required by neural progenitor cells expressing its receptor VEGFR-3...
  75. ncbi An important role of lymphatic vessels in the control of UVB-induced edema formation and inflammation
    Kentaro Kajiya
    J Invest Dermatol 126:919-21. 2006
  76. pmc Transcapillary fluid balance consequences of missing initial lymphatics studied in a mouse model of primary lymphoedema
    Tine V Karlsen
    Department of Biomedicine, University of Bergen, Jonas Lies vei 91, N 5009 Bergen, Norway
    J Physiol 574:583-96. 2006
    ..of transcapillary fluid filtration and inflammatory mediators in the interstitial fluid in genetically engineered Chy mice, a model for primary congenital lymphoedema (Milroy's disease)...
  77. ncbi Upregulation of soluble vascular endothelial growth factor receptor 1 contributes to angiogenesis defects in the placenta of alpha 2B-adrenoceptor deficient mice
    Verena Muthig
    Institute of Experimental and Clinical Pharmacology, University of Freiburg, Albertstrasse 25, 79104 Freiburg, Germany
    Circ Res 101:682-91. 2007
    ....
  78. ncbi Effects of acute exercise, exercise training, and diabetes on the expression of lymphangiogenic growth factors and lymphatic vessels in skeletal muscle
    Riikka Kivela
    LIKES Research Center for Sport and Health Sciences, University of Jyvaskyla, Rautpohjankatu 8a, FIN 40700 Jyväskylä, Finland
    Am J Physiol Heart Circ Physiol 293:H2573-9. 2007
    ..Diabetes increased the expression of VEGF-D in skeletal muscle, and this increase may be related to muscle fiber damage...
  79. pmc Adrenomedullin signaling is necessary for murine lymphatic vascular development
    Kimberly L Fritz-Six
    Department of Cell and Molecular Physiology, The University of North Carolina, Chapel Hill, North Carolina 27599, USA
    J Clin Invest 118:40-50. 2008
    ..Collectively, our studies identify a class of genes involved in lymphangiogenesis that represent a pharmacologically tractable system for the treatment of lymphedema or inhibition of tumor metastasis...
  80. pmc Emilin1 deficiency causes structural and functional defects of lymphatic vasculature
    Carla Danussi
    Division of Experimental Oncology 2, Department of Molecular Oncology and Translational Research, CRO IRCCS, Aviano, Pordenone, Italy
    Mol Cell Biol 28:4026-39. 2008
    ..The phenotype displayed by Emilin1(-/-) mice is the first abnormal lymphatic phenotype associated with the deficiency of an ECM protein and identifies EMILIN1 as a novel local regulator of lymphangiogenesis...
  81. doi Coronary development is regulated by ATP-dependent SWI/SNF chromatin remodeling component BAF180
    Xuling Huang
    Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Richard Simches Research Center, 185 Cambridge Street, Boston, MA 02114, USA
    Dev Biol 319:258-66. 2008
    ..Together, these data reveal for the first time that BAF180 is critical for coronary vessel formation...
  82. pmc Lymph sacs are not required for the initiation of lymph node formation
    Mark F Vondenhoff
    Department of Molecular Cell Biology and Immunology, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam, The Netherlands
    Development 136:29-34. 2009
    ..5 Prox1 conditional mutant embryos, which have defective lymph sacs. However, subsequent clustering of hematopoietic cells within these developing lymph nodes is less efficient...
  83. pmc Inflammation induces lymphangiogenesis through up-regulation of VEGFR-3 mediated by NF-kappaB and Prox1
    Michael J Flister
    Department of Medical Microbiology, Immunology, and Cell Biology, Southern Illinois University School of Medicine, Springfield, IL 62794 9626, USA
    Blood 115:418-29. 2010
    ..This, in turn, enhances the responsiveness of preexisting lymphatic endothelium to VEGFR-3 binding factors, VEGF-C and VEGF-D, ultimately resulting in robust lymphangiogenesis...
  84. doi Targeting lymphatic vessel activation and CCL21 production by vascular endothelial growth factor receptor-3 inhibition has novel immunomodulatory and antiarteriosclerotic effects in cardiac allografts
    Antti I Nykänen
    Cardiopulmonary Research Group, Transplantation Laboratory, Haartman Institute, FI 00014 University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland
    Circulation 121:1413-22. 2010
    ..We aimed to determine the role of lymphatic vessels and their principal growth signaling pathway, vascular endothelial growth factor (VEGF)-C/D/VEGFR-3, during acute and chronic rejection in cardiac allografts...
  85. pmc Direct transcriptional regulation of neuropilin-2 by COUP-TFII modulates multiple steps in murine lymphatic vessel development
    Fu Jung Lin
    Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA
    J Clin Invest 120:1694-707. 2010
    ..Thus, COUP-TFII is a critical factor that controls lymphangiogenesis in embryonic development and tumorigenesis in adults...
  86. pmc Tbx1 regulates Vegfr3 and is required for lymphatic vessel development
    Li Chen
    Program of Cardiovascular Sciences, Baylor College of Medicine, Houston, TX 77030, USA
    J Cell Biol 189:417-24. 2010
    ..unexpectedly, that Tbx1 plays a critical role in lymphatic vessel development and regulates the expression of Vegfr3, a gene that is essential for lymphangiogenesis...
  87. doi The Wnt/beta-catenin pathway modulates vascular remodeling and specification by upregulating Dll4/Notch signaling
    Monica Corada
    IFOM, The FIRC Institute of Molecular Oncology Foundation, 20139 Milan, Italy
    Dev Cell 18:938-49. 2010
    ..We propose that early and sustained beta-catenin signaling prevents correct endothelial cell differentiation, altering vascular remodeling and arteriovenous specification...
  88. pmc Characterization of Prox1 and VEGFR-3 expression and lymphatic phenotype in normal organs of mice lacking p50 subunit of NF-κB
    Michael J Flister
    Department of Medical Microbiology, Immunology, and Cell Biology, Southern Illinois University School of Medicine, Springfield, Illinois 62794 9626, USA
    Microcirculation 18:85-101. 2011
    ..To elucidate the role of p50 in lymphatic vasculature, we compared LVD and phenotype in p50 KO and WT mice...
  89. pmc Angiogenic sprouting into neural tissue requires Gpr124, an orphan G protein-coupled receptor
    Keith D Anderson
    VelociGene Division, Regeneron Pharmaceuticals, Inc, Tarrytown, NY 10591, USA
    Proc Natl Acad Sci U S A 108:2807-12. 2011
    ..These results represent a unique function attributed to a long N-terminal group B-type G protein-coupled receptor in a mammalian system...
  90. pmc Soluble vascular endothelial growth factor receptor-3 suppresses lymphangiogenesis and lymphatic metastasis in bladder cancer
    Hanseul Yang
    National Research Laboratory of Vascular Biology and Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, 305 701, Republic of Korea
    Mol Cancer 10:36. 2011
    ..The aim of this study is to elucidate underlying mechanisms of how expanded lymphatic vessels and tumor microenvironment interacts each other and to find effective therapeutic options to inhibit lymphatic metastasis...
  91. pmc Stepwise arteriovenous fate acquisition during mammalian vasculogenesis
    Diana C Chong
    Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, Texas, USA
    Dev Dyn 240:2153-65. 2011
    ..Together, our results provide a first spatiotemporal analysis of mammalian AV cell fate establishment and anatomy, as well as a delineation of a molecular toolkit for analysis of arteries and veins during early vessel development...
  92. pmc VEGFR-3 controls tip to stalk conversion at vessel fusion sites by reinforcing Notch signalling
    Tuomas Tammela
    Molecular Cancer Biology Laboratory, Institute for Molecular Medicine Finland, Research Programs Unit and Department of Pathology, Haartman Institute, Biomedicum Helsinki, PO Box 63 Haartmaninkatu 8, 00014 University of Helsinki, Finland
    Nat Cell Biol 13:1202-13. 2011
    ..Surprisingly, we found that endothelial deletion of Vegfr3, but not VEGFR-3-blocking antibodies, postnatally led to excessive angiogenic sprouting and branching, and ..
  93. ncbi Molecular cloning of murine FLT and FLT4
    H Finnerty
    Genetics Institute, Inc, Cambridge, Massachusetts 02140
    Oncogene 8:2293-8. 1993
    ..A novel RTK, called FLT4, and the murine homologue of FLT were found, and their PCR fragment sequences were used to isolate larger cDNA ..
  94. ncbi Targeted deficiency or cytosolic truncation of the VE-cadherin gene in mice impairs VEGF-mediated endothelial survival and angiogenesis
    P Carmeliet
    Center for Transgene Technology and Gene Therapy, Flanders Interuniversity Institute for Biotechnology, Leuven, Belgium
    Cell 98:147-57. 1999
    ..Thus, VE-cadherin/ beta-catenin signaling controls endothelial survival...
  95. ncbi Transgenic mouse models in angiogenesis and cardiovascular disease
    P Carmeliet
    Center for Transgene Technology and Gene Therapy, Flanders Interuniversity Institute for Biotechnology, KU Leuven, Leuven, B 3000, Belgium
    J Pathol 190:387-405. 2000
    ..A selected number of molecules that have been studied in the authors' laboratory will be reviewed in more detail...
  96. ncbi Involvement of vascular endothelial growth factor receptor-3 in maintenance of integrity of endothelial cell lining during tumor angiogenesis
    H Kubo
    Departments of Gastroenterological Surgery and Molecular Genetics, Graduate School of Medicine, Kyoto University, Kyoto, Japan
    Blood 96:546-53. 2000
    ..Moreover, our results suggest that the VEGF-C/VEGFR-3 pathway may serve another candidate target for cancer therapy. (Blood. 2000;96:546-553)..
  97. ncbi Mesenchymal expression of vascular endothelial growth factors D and A defines vascular patterning in developing lung
    James M Greenberg
    Division of Pulmonary Biology, Children s Hospital Research Foundation, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229, USA
    Dev Dyn 224:144-53. 2002
    ..Our results demonstrate unique temporal and spatial expression of VEGF-D and specific VEGF-A isoforms during lung development and suggest these related factors have distinct functions in vascular and lymphatic patterning of the lung...
  98. ncbi Suppression of VEGFR-3 signaling inhibits lymph node metastasis in gastric cancer
    Kenji Shimizu
    Department of Gastroenterological Surgery, Graduate School of Medicine, Kyoto University, Sakyo ku, Kyoto 606 8507, Japan
    Cancer Sci 95:328-33. 2004
    ..Antilymphangiogenesis by inhibiting VEGFR-3 signaling could provide a potential strategy for the prevention of lymph node metastasis in gastric cancer...
  99. pmc Membrane fixation of vascular endothelial growth factor receptor 1 ligand-binding domain is important for vasculogenesis and angiogenesis in mice
    Sachie Hiratsuka
    Division of Genetics, Institute of Medical Science, University of Tokyo, Tokyo 108 8639, Japan
    Mol Cell Biol 25:346-54. 2005
    ..These results strongly suggest that the membrane-fixed ligand-binding region of VEGFR1 traps VEGF for the appropriate regulation of VEGF signaling in vascular endothelial cells during early embryogenesis...