Genomes and Genes
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
Publications121 found, 100 shown here
- Vascular endothelial growth factor receptor-3 in hypoxia-induced vascular developmentIngrid 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...
- Spreds are essential for embryonic lymphangiogenesis by regulating vascular endothelial growth factor receptor 3 signalingKoji 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...
- VEGFR-3/Flt-4 mediates proliferation and chemotaxis in glial precursor cellsSandra 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...
- Suppression of lymphangiogenesis induced by Flt-4 antibody in gastric low-grade mucosa-associated lymphoid tissue lymphoma by Helicobacter heilmannii infectionMasahiko 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...
- ALK5 phosphorylation of the endoglin cytoplasmic domain regulates Smad1/5/8 signaling and endothelial cell migrationBridgette 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...
- Failure of blood-island formation and vasculogenesis in Flk-1-deficient miceF 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...
- Role of the Flt-1 receptor tyrosine kinase in regulating the assembly of vascular endotheliumG 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...
- Expression of the fms-like tyrosine kinase 4 gene becomes restricted to lymphatic endothelium during developmentA Kaipainen
Molecular Cancer Biology Laboratory, University of Helsinki, Finland
Proc Natl Acad Sci U S A 92:3566-70. 1995We 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...
- VEGF-C receptor binding and pattern of expression with VEGFR-3 suggests a role in lymphatic vascular developmentE 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 ..
- Cardiovascular failure in mouse embryos deficient in VEGF receptor-3D 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...
- Prox1 function is required for the development of the murine lymphatic systemJ 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...
- Signalling via vascular endothelial growth factor receptor-3 is sufficient for lymphangiogenesis in transgenic miceT 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...
- The specificity of receptor binding by vascular endothelial growth factor-d is different in mouse and manM 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...
- A model for gene therapy of human hereditary lymphedemaM 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, ..
- An essential role for Prox1 in the induction of the lymphatic endothelial cell phenotypeJeffrey 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...
- Blockade of vascular endothelial growth factor receptor-3 signaling inhibits fibroblast growth factor-2-induced lymphangiogenesis in mouse corneaHajime 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...
- Abnormal lymphatic vessel development in neuropilin 2 mutant miceLi 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...
- Modulation of VEGFR-2-mediated endothelial-cell activity by VEGF-C/VEGFR-3Kazuyoshi 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...
- Novel expression of vascular endothelial growth factor receptor (VEGFR)-3 and VEGF-C on corneal dendritic cellsPedram 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...
- Vascular endothelial growth factor C is required for sprouting of the first lymphatic vessels from embryonic veinsMarika 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...
- Complete and specific inhibition of adult lymphatic regeneration by a novel VEGFR-3 neutralizing antibodyBronislaw Pytowski
Molecular and Cellular Biology, ImClone Systems, New York, NY, USA
J Natl Cancer Inst 97:14-21. 2005New 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...
- PDZ interaction site in ephrinB2 is required for the remodeling of lymphatic vasculatureTaija 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...
- Angiopoietin-1 promotes lymphatic sprouting and hyperplasiaTuomas 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...
- Lymphangiogenic growth factor responsiveness is modulated by postnatal lymphatic vessel maturationTerhi 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...
- Cooperative and redundant roles of VEGFR-2 and VEGFR-3 signaling in adult lymphangiogenesisJeremy 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...
- Prox1 induces lymphatic endothelial differentiation via integrin alpha9 and other signaling cascadesKoichi 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)...
- A Gata2 intronic enhancer confers its pan-endothelia-specific regulationMelin 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...
- Distinct vascular endothelial growth factor signals for lymphatic vessel enlargement and sproutingMaria 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...
- Lymphatic development in mouse small intestineKyung 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...
- Expression of the hyaluronan receptor LYVE-1 is not restricted to the lymphatic vasculature; LYVE-1 is also expressed on embryonic blood vesselsEmma 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...
- Blocking VEGFR-3 suppresses angiogenic sprouting and vascular network formationTuomas 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...
- NFATc1 regulates lymphatic endothelial developmentRishikesh 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...
- FOXC2 controls formation and maturation of lymphatic collecting vessels through cooperation with NFATc1Camilla 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...
- Integrin-alpha9 is required for fibronectin matrix assembly during lymphatic valve morphogenesisEleni 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...
- 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 arthritisRuolin 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...
- Neuropilin-2 mediates VEGF-C-induced lymphatic sprouting together with VEGFR3Yunling 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.
- Novel function for blood platelets and podoplanin in developmental separation of blood and lymphatic circulationPavel 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...
- H-, N- and Kras cooperatively regulate lymphatic vessel growth by modulating VEGFR3 expression in lymphatic endothelial cells in miceTaeko 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 ..
- VEGFR-3 ligand-binding and kinase activity are required for lymphangiogenesis but not for angiogenesisLuqing 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))...
- Lymphatic ontogeny and effect of hypoplasia in developing lungRishikesh 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...
- CCBE1 is essential for mammalian lymphatic vascular development and enhances the lymphangiogenic effect of vascular endothelial growth factor-C in vivoFrank 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...
- Prox1 dosage controls the number of lymphatic endothelial cell progenitors and the formation of the lymphovenous valvesR 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...
- Mechanoinduction of lymph vessel expansionLara 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...
- Mechanotransduction, PROX1, and FOXC2 cooperate to control connexin37 and calcineurin during lymphatic-valve formationAmélie 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...
- Defective valves and abnormal mural cell recruitment underlie lymphatic vascular failure in lymphedema distichiasisTatiana 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)...
- Deletion of vascular endothelial growth factor C (VEGF-C) and VEGF-D is not equivalent to VEGF receptor 3 deletion in mouse embryosPaula 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...
- Foxc2 is expressed in developing lymphatic vessels and other tissues associated with lymphedema-distichiasis syndromeSusan 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....
- Abnormal embryonic lymphatic vessel development in Tie1 hypomorphic miceXianghu 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...
- Embryonic vascular endothelial cells are malleable to reprogramming via Prox1 to a lymphatic gene signatureHarold 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...
- Genes regulating lymphangiogenesis control venous valve formation and maintenance in miceEleni 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...
- Blocking Fibroblast Growth Factor receptor signaling inhibits tumor growth, lymphangiogenesis, and metastasisFrederic Larrieu-Lahargue
Laboratoire de l Angiogenèse et du Microenvironement des Cancers, Universite de Bordeaux, Talence, France
PLoS ONE 7:e39540. 2012....
- Vascular endothelial growth factor receptor-2 promotes the development of the lymphatic vasculatureMichael 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. ..
- Molecular identification of venous progenitors in the dorsal aorta reveals an aortic origin for the cardinal vein in mammalsHenrik 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. ..
- VEGFR3 does not sustain retinal angiogenesis without VEGFR2Georgia 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...
- The matricellular protein CCN1 controls retinal angiogenesis by targeting VEGF, Src homology 2 domain phosphatase-1 and Notch signalingHemabindu 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. ..
- Defective lymphatic valve development and chylothorax in mice with a lymphatic-specific deletion of Connexin43Stephanie 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...
- Involvement of insulin-like growth factor 2 in angiogenic factor transcription in Bi-maternal mouse conceptusesManabu 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) ..
- ALK1 signaling regulates early postnatal lymphatic vessel developmentKyle 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...
- Impaired angiogenesis and altered Notch signaling in mice overexpressing endothelial Egfl7Donna 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...
- Combined blockade of VEGFR-2 and VEGFR-3 inhibits inflammatory lymphangiogenesis in early and middle stagesDon 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...
- Mirtron microRNA-1236 inhibits VEGFR-3 signaling during inflammatory lymphangiogenesisDennis 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...
- Notch-dependent VEGFR3 upregulation allows angiogenesis without VEGF-VEGFR2 signallingRui 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...
- In vivo imaging of lymphatic vessels in development, wound healing, inflammation, and tumor metastasisInés 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 ..
- Target gene analysis by microarrays and chromatin immunoprecipitation identifies HEY proteins as highly redundant bHLH repressorsJulia 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...
- Characterization and therapeutic potential of induced pluripotent stem cell-derived cardiovascular progenitor cellsAli 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...
- Soluble vascular endothelial growth factor receptor 3 is essential for corneal alymphaticityNirbhai 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 ..
- Chromosomal localization of FLT4, a novel receptor-type tyrosine kinase geneF 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...
- Characterization of murine Flt4 ligand/VEGF-CL J Fitz
Genetics Institute, Inc, Cambridge, Massachusetts 02140, USA
Oncogene 15:613-8. 1997Flt4 is a receptor protein tyrosine kinase that is expressed in the adult lymphatic endothelium and high endothelial venules...
- The transcription factor MEF2C-null mouse exhibits complex vascular malformations and reduced cardiac expression of angiopoietin 1 and VEGFW Bi
Division of Cardiology, University of Texas Medical School at Houston, Houston, Texas, 77030, USA
Dev Biol 211:255-67. 1999....
- VEGF-C signaling pathways through VEGFR-2 and VEGFR-3 in vasculoangiogenesis and hematopoiesisK 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)..
- Erk5 null mice display multiple extraembryonic vascular and embryonic cardiovascular defectsChristopher 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...
- Expression of vascular endothelial growth factor receptor-3 (VEGFR-3) in the conjunctiva--a potential link between lymphangiogenesis and leukocyte trafficking on the ocular surfacePedram 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
- Angiopoietin-1 promotes LYVE-1-positive lymphatic vessel formationTohru 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...
- VEGF-C is a trophic factor for neural progenitors in the vertebrate embryonic brainBarbara 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...
- An important role of lymphatic vessels in the control of UVB-induced edema formation and inflammationKentaro Kajiya
J Invest Dermatol 126:919-21. 2006
- Transcapillary fluid balance consequences of missing initial lymphatics studied in a mouse model of primary lymphoedemaTine 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)...
- Upregulation of soluble vascular endothelial growth factor receptor 1 contributes to angiogenesis defects in the placenta of alpha 2B-adrenoceptor deficient miceVerena Muthig
Institute of Experimental and Clinical Pharmacology, University of Freiburg, Albertstrasse 25, 79104 Freiburg, Germany
Circ Res 101:682-91. 2007....
- Effects of acute exercise, exercise training, and diabetes on the expression of lymphangiogenic growth factors and lymphatic vessels in skeletal muscleRiikka 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...
- Adrenomedullin signaling is necessary for murine lymphatic vascular developmentKimberly 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...
- Emilin1 deficiency causes structural and functional defects of lymphatic vasculatureCarla 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...
- Coronary development is regulated by ATP-dependent SWI/SNF chromatin remodeling component BAF180Xuling 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...
- Lymph sacs are not required for the initiation of lymph node formationMark 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...
- Inflammation induces lymphangiogenesis through up-regulation of VEGFR-3 mediated by NF-kappaB and Prox1Michael 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...
- Targeting lymphatic vessel activation and CCL21 production by vascular endothelial growth factor receptor-3 inhibition has novel immunomodulatory and antiarteriosclerotic effects in cardiac allograftsAntti 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...
- Direct transcriptional regulation of neuropilin-2 by COUP-TFII modulates multiple steps in murine lymphatic vessel developmentFu 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...
- Tbx1 regulates Vegfr3 and is required for lymphatic vessel developmentLi 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...
- The Wnt/beta-catenin pathway modulates vascular remodeling and specification by upregulating Dll4/Notch signalingMonica 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...
- Characterization of Prox1 and VEGFR-3 expression and lymphatic phenotype in normal organs of mice lacking p50 subunit of NF-κBMichael 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...
- Angiogenic sprouting into neural tissue requires Gpr124, an orphan G protein-coupled receptorKeith 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...
- Soluble vascular endothelial growth factor receptor-3 suppresses lymphangiogenesis and lymphatic metastasis in bladder cancerHanseul 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...
- Stepwise arteriovenous fate acquisition during mammalian vasculogenesisDiana 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...
- VEGFR-3 controls tip to stalk conversion at vessel fusion sites by reinforcing Notch signallingTuomas 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 ..
- Molecular cloning of murine FLT and FLT4H 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 ..
- Targeted deficiency or cytosolic truncation of the VE-cadherin gene in mice impairs VEGF-mediated endothelial survival and angiogenesisP 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...
- Transgenic mouse models in angiogenesis and cardiovascular diseaseP 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...
- Involvement of vascular endothelial growth factor receptor-3 in maintenance of integrity of endothelial cell lining during tumor angiogenesisH 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)..
- Mesenchymal expression of vascular endothelial growth factors D and A defines vascular patterning in developing lungJames 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...
- Suppression of VEGFR-3 signaling inhibits lymph node metastasis in gastric cancerKenji 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...
- Membrane fixation of vascular endothelial growth factor receptor 1 ligand-binding domain is important for vasculogenesis and angiogenesis in miceSachie 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...