Gene Symbol: Kdr
Description: kinase insert domain protein receptor
Alias: 6130401C07, Flk-1, Flk1, Krd-1, Ly73, VEGFR-2, VEGFR2, orv, sVEGFR-2, vascular endothelial growth factor receptor 2, VEGF receptor-2, fetal liver kinase 1, kinase NYK, protein-tyrosine kinase receptor flk-1, soluble vascular endothelial growth factor receptor 2, vascular endothelial growth factor receptor-3
Species: mouse
Products:     Kdr

Top Publications

  1. Misfeldt A, Boyle S, Tompkins K, Bautch V, Labosky P, Baldwin H. Endocardial cells are a distinct endothelial lineage derived from Flk1+ multipotent cardiovascular progenitors. Dev Biol. 2009;333:78-89 pubmed publisher
    ..Furthermore, a population of Flk1+ cardiovascular progenitors, distinct from hemangioblast precursors, represents a mesodermal precursor of the ..
  2. Fantin A, Herzog B, Mahmoud M, Yamaji M, Plein A, Denti L, et al. Neuropilin 1 (NRP1) hypomorphism combined with defective VEGF-A binding reveals novel roles for NRP1 in developmental and pathological angiogenesis. Development. 2014;141:556-62 pubmed publisher
    ..evidence supports a model for NRP1 function in which VEGF binding induces complex formation between NRP1 and VEGFR2 to enhance endothelial VEGF signalling...
  3. Yang Y, Zhang Y, Cao Z, Ji H, Yang X, Iwamoto H, et al. Anti-VEGF- and anti-VEGF receptor-induced vascular alteration in mouse healthy tissues. Proc Natl Acad Sci U S A. 2013;110:12018-23 pubmed publisher
    ..Understanding anti-VEGF drug-induced vascular alterations in healthy tissues is crucial to minimize and even to avoid adverse effects produced by currently used anti-VEGF-specific drugs. ..
  4. Milgrom Hoffman M, Harrelson Z, Ferrara N, Zelzer E, Evans S, Tzahor E. The heart endocardium is derived from vascular endothelial progenitors. Development. 2011;138:4777-87 pubmed publisher
    ..To gain deeper insight into this heterogeneity, we conditionally ablated Flk1 in distinct cardiovascular progenitor populations; FLK1 is required in vivo for formation of the endocardium in the ..
  5. Alder O, Lavial F, Helness A, Brookes E, Pinho S, Chandrashekran A, et al. Ring1B and Suv39h1 delineate distinct chromatin states at bivalent genes during early mouse lineage commitment. Development. 2010;137:2483-92 pubmed publisher
  6. Nilsson I, Bahram F, Li X, Gualandi L, Koch S, Jarvius M, et al. VEGF receptor 2/-3 heterodimers detected in situ by proximity ligation on angiogenic sprouts. EMBO J. 2010;29:1377-88 pubmed publisher
    ..They exert their effects by dimerization and activation of the cognate receptors VEGFR2 and VEGFR3. Here, we have used in situ proximity ligation to detect receptor complexes in intact endothelial cells...
  7. Ferdous A, Caprioli A, Iacovino M, Martin C, Morris J, Richardson J, et al. Nkx2-5 transactivates the Ets-related protein 71 gene and specifies an endothelial/endocardial fate in the developing embryo. Proc Natl Acad Sci U S A. 2009;106:814-9 pubmed publisher
    ..Collectively, our results uncover a novel functional role for Nkx2-5 and define a transcriptional network that specifies an endocardial/endothelial fate in the developing heart and embryo. ..
  8. Trindade A, Kumar S, Scehnet J, Lopes da Costa L, Becker J, Jiang W, et al. Overexpression of delta-like 4 induces arterialization and attenuates vessel formation in developing mouse embryos. Blood. 2008;112:1720-9 pubmed publisher
    ..These results establish the role of Dll4 in arterial identity determination, and regulation of angiogenesis subject to dose and location. ..
  9. Pierreux C, Cordi S, Hick A, Achouri Y, Ruiz de Almodovar C, Prevot P, et al. Epithelial: Endothelial cross-talk regulates exocrine differentiation in developing pancreas. Dev Biol. 2010;347:216-27 pubmed publisher
    ..In conclusion, our data suggest that, in developing pancreas, epithelial production of VEGF-A determines the spatial organization of endothelial cells which, in turn, limit acinar differentiation of the epithelium. ..

More Information


  1. Albuquerque R, Hayashi T, Cho W, Kleinman M, Dridi S, Takeda A, et al. Alternatively spliced vascular endothelial growth factor receptor-2 is an essential endogenous inhibitor of lymphatic vessel growth. Nat Med. 2009;15:1023-30 pubmed publisher
  2. Li Z, Huang H, Boland P, Dominguez M, Burfeind P, Lai K, et al. Embryonic stem cell tumor model reveals role of vascular endothelial receptor tyrosine phosphatase in regulating Tie2 pathway in tumor angiogenesis. Proc Natl Acad Sci U S A. 2009;106:22399-404 pubmed publisher
    ..Endothelial differentiation in the ES teratoma model allows gene-targeting methods to be used in the study of tumor angiogenesis. ..
  3. Gentile C, Muise Helmericks R, Drake C. VEGF-mediated phosphorylation of eNOS regulates angioblast and embryonic endothelial cell proliferation. Dev Biol. 2013;373:163-75 pubmed publisher
    ..Taken together, our findings suggest that VEGF-mediated eNOS phosphorylation on Ser1177 regulates angioblast and EEC division, which underlies the formation of blood vessels and vascular networks. ..
  4. Teichert A, Scott J, Robb G, Zhou Y, Zhu S, Lem M, et al. Endothelial nitric oxide synthase gene expression during murine embryogenesis: commencement of expression in the embryo occurs with the establishment of a unidirectional circulatory system. Circ Res. 2008;103:24-33 pubmed publisher
    ..In summary, transcriptional activity of the eNOS gene in the murine circulatory system occurred following the establishment of embryonic blood flow. Thus, the eNOS gene is a late-onset gene in endothelial ontogeny. ..
  5. Scheppke L, Aguilar E, Gariano R, Jacobson R, Hood J, Doukas J, et al. Retinal vascular permeability suppression by topical application of a novel VEGFR2/Src kinase inhibitor in mice and rabbits. J Clin Invest. 2008;118:2337-46 pubmed publisher
    ..administration of VEGF in mice was abolished by systemic or topical delivery of what we believe is a novel VEGFR2/Src kinase inhibitor; this was confirmed in rabbits...
  6. Sawamiphak S, Seidel S, Essmann C, Wilkinson G, Pitulescu M, Acker T, et al. Ephrin-B2 regulates VEGFR2 function in developmental and tumour angiogenesis. Nature. 2010;465:487-91 pubmed publisher
    ..Importantly, internalization of VEGFR2 is necessary for activation and downstream signalling of the receptor and is required for VEGF-induced tip cell ..
  7. Shawber C, Funahashi Y, Francisco E, Vorontchikhina M, Kitamura Y, Stowell S, et al. Notch alters VEGF responsiveness in human and murine endothelial cells by direct regulation of VEGFR-3 expression. J Clin Invest. 2007;117:3369-82 pubmed
    ..These results demonstrate that Notch1 and VEGFR-3 interact genetically, that Notch directly induces VEGFR-3 in blood endothelial cells to regulate vascular development, and that Notch may function in tumor lymphangiogenesis. ..
  8. Li X, Edholm D, Lanner F, Breier G, Farnebo F, Dimberg A, et al. Lentiviral rescue of vascular endothelial growth factor receptor-2 expression in flk1-/- embryonic stem cells shows early priming of endothelial precursors. Stem Cells. 2007;25:2987-95 pubmed
    ..We used lentiviral transduction to reconstitute VEGFR-2 expression in flk1-/- embryonic stem (ES) cells...
  9. Bernatchez P, Acevedo L, Fernandez Hernando C, Murata T, Chalouni C, Kim J, et al. Myoferlin regulates vascular endothelial growth factor receptor-2 stability and function. J Biol Chem. 2007;282:30745-53 pubmed
    ..These data are the first to report novel biological activities for myoferlin and reveal the role of membrane integrity to VEGF signaling. ..
  10. Okuno Y, Nakamura Ishizu A, Kishi K, Suda T, Kubota Y. Bone marrow-derived cells serve as proangiogenic macrophages but not endothelial cells in wound healing. Blood. 2011;117:5264-72 pubmed publisher
    ..Our data show that the proangiogenic effects of macrophages, but not the endothelial differentiation, are the major contribution of BMDCs in wound healing. ..
  11. Ruiz de Almodovar C, Fabre P, Knevels E, Coulon C, Segura I, Haddick P, et al. VEGF mediates commissural axon chemoattraction through its receptor Flk1. Neuron. 2011;70:966-78 pubmed publisher
    ..Inactivation of Vegf in the floor plate or of its receptor Flk1 in commissural neurons causes axon guidance defects, whereas Flk1 blockade inhibits turning of axons to VEGF in ..
  12. Ishitobi H, Wakamatsu A, Liu F, Azami T, Hamada M, Matsumoto K, et al. Molecular basis for Flk1 expression in hemato-cardiovascular progenitors in the mouse. Development. 2011;138:5357-68 pubmed publisher
    The mouse Flk1 gene is expressed in various mesodermal progenitor cells of developing embryos...
  13. Ruiz de Almodovar C, Coulon C, Salin P, Knevels E, Chounlamountri N, Poesen K, et al. Matrix-binding vascular endothelial growth factor (VEGF) isoforms guide granule cell migration in the cerebellum via VEGF receptor Flk1. J Neurosci. 2010;30:15052-66 pubmed publisher
    ..GCs express the VEGF receptor Flk1, and are chemoattracted by VEGF, whose levels are higher in the PCL than EGL...
  14. Wareing S, Mazan A, Pearson S, Göttgens B, Lacaud G, Kouskoff V. The Flk1-Cre-mediated deletion of ETV2 defines its narrow temporal requirement during embryonic hematopoietic development. Stem Cells. 2012;30:1521-31 pubmed publisher
    ..Using cre-mediated deletion of ETV2, we demonstrate that ETV2 is acting prior to or at the time of FLK1 expression in mesodermal precursors to initiate the hematopoietic and endothelial program...
  15. Sano K, Katsuta O, Shirae S, Kubota Y, Ema M, Suda T, et al. Flt1 and Flk1 mediate regulation of intraocular pressure and their double heterozygosity causes the buphthalmia in mice. Biochem Biophys Res Commun. 2012;420:422-7 pubmed publisher
    Flt1 and Flk1 are receptor tyrosine kinases for vascular endothelial growth factor-A which play a crucial role in physiological and pathological angiogenesis...
  16. Lanahan A, Hermans K, Claes F, Kerley Hamilton J, Zhuang Z, Giordano F, et al. VEGF receptor 2 endocytic trafficking regulates arterial morphogenesis. Dev Cell. 2010;18:713-24 pubmed publisher
    ..Here, we show that this occurs due to delayed trafficking of VEGFR2-containing endosomes that exposes internalized VEGFR2 to selective dephosphorylation by PTP1b on Y(1175) site...
  17. Red Horse K, Ueno H, Weissman I, Krasnow M. Coronary arteries form by developmental reprogramming of venous cells. Nature. 2010;464:549-53 pubmed publisher
    ..Understanding this new reprogramming process and identifying the endogenous signals should suggest more natural ways of engineering coronary bypass grafts and revascularizing the heart. ..
  18. Huang H, Shen J, Vinores S. Blockade of VEGFR1 and 2 suppresses pathological angiogenesis and vascular leakage in the eye. PLoS ONE. 2011;6:e21411 pubmed publisher
    ..Neutralizing antibodies specific for mouse VEGFR1 (MF1) and VEGFR2 (DC101) were administrated systemically...
  19. Xu Y, Yuan L, Mak J, Pardanaud L, Caunt M, Kasman I, et al. Neuropilin-2 mediates VEGF-C-induced lymphatic sprouting together with VEGFR3. J Cell Biol. 2010;188:115-30 pubmed publisher
    ..To investigate whether this defect depends on Nrp2 interaction with VEGF receptor 2 (VEGFR2) and/or 3, we intercrossed heterozygous mice lacking one allele of these receptors...
  20. Planas Paz L, Strilic B, Goedecke A, Breier G, Fassler R, Lammert E. Mechanoinduction of lymph vessel expansion. EMBO J. 2012;31:788-804 pubmed publisher
    ..Thus, we propose a new and physiologically relevant mode of VEGFR3 activation, which is based on mechanotransduction and is essential for normal development and fluid homeostasis in a mammalian embryo...
  21. Benedito R, Rocha S, Woeste M, Zamykal M, Radtke F, Casanovas O, et al. Notch-dependent VEGFR3 upregulation allows angiogenesis without VEGF-VEGFR2 signalling. Nature. 2012;484:110-4 pubmed publisher
    ..combination with inhibitors in vivo, that DLL4 protein expression in retinal tip cells is only weakly modulated by VEGFR2 signalling...
  22. Lanahan A, Zhang X, Fantin A, Zhuang Z, Rivera Molina F, Speichinger K, et al. The neuropilin 1 cytoplasmic domain is required for VEGF-A-dependent arteriogenesis. Dev Cell. 2013;25:156-68 pubmed publisher
    ..The arteriogenic defect was traced to the absence of a PDZ-dependent interaction between NRP1 and VEGF receptor 2 (VEGFR2) complex and synectin, which delayed trafficking of endocytosed VEGFR2 from Rab5+ to EAA1+ endosomes...
  23. Fantin A, Vieira J, Plein A, Denti L, Fruttiger M, Pollard J, et al. NRP1 acts cell autonomously in endothelium to promote tip cell function during sprouting angiogenesis. Blood. 2013;121:2352-62 pubmed publisher
    ..Previous in vitro experiments identified NRP1 interactions with VEGF-A's main signaling receptor VEGFR2 within endothelial cells, but also between nonendothelial NRP1 and endothelial VEGFR2...
  24. Cai C, Martin J, Sun Y, Cui L, Wang L, Ouyang K, et al. A myocardial lineage derives from Tbx18 epicardial cells. Nature. 2008;454:104-8 pubmed publisher
    ..The pluripotency of Tbx18 proepicardial cells provides a theoretical framework for applying these progenitors to effect cardiac repair and regeneration. ..
  25. Gavard J, Patel V, Gutkind J. Angiopoietin-1 prevents VEGF-induced endothelial permeability by sequestering Src through mDia. Dev Cell. 2008;14:25-36 pubmed publisher
    ..This ultimately deprives VEGF receptors of an essential molecule required for promoting the disruption of endothelial cell-cell contacts and paracellular permeability. ..
  26. Kataoka H, Hayashi M, Nakagawa R, Tanaka Y, Izumi N, Nishikawa S, et al. Etv2/ER71 induces vascular mesoderm from Flk1+PDGFR?+ primitive mesoderm. Blood. 2011;118:6975-86 pubmed publisher
    ..We propose that Flk-1(+)/PDGFR?(+) primitive mesoderm is committed into Flk-1(+)/PDGFR?(-) vascular mesoderm through Etv2 and that up-regulation of Etv2 by VEGF promotes this commitment...
  27. Sabine A, Agalarov Y, Maby El Hajjami H, Jaquet M, Hägerling R, Pollmann C, et al. Mechanotransduction, PROX1, and FOXC2 cooperate to control connexin37 and calcineurin during lymphatic-valve formation. Dev Cell. 2012;22:430-45 pubmed publisher
    ..Our results also provide molecular insights into the role of endothelial cell identity in the regulation of vascular mechanotransduction. ..
  28. Bekhite M, Finkensieper A, Binas S, Müller J, Wetzker R, Figulla H, et al. VEGF-mediated PI3K class IA and PKC signaling in cardiomyogenesis and vasculogenesis of mouse embryonic stem cells. J Cell Sci. 2011;124:1819-30 pubmed publisher
    ..Akt downstream of PI3K is involved in both cardiomyogenesis and vasculogenesis, whereas PKC is involved only in vasculogenesis. ..
  29. Liu F, Kang I, Park C, Chang L, Wang W, Lee D, et al. ER71 specifies Flk-1+ hemangiogenic mesoderm by inhibiting cardiac mesoderm and Wnt signaling. Blood. 2012;119:3295-305 pubmed publisher
    ..We provide the molecular basis for the antagonistic relationship between hemangiogenic and cardiogenic mesoderm specification by ER71 and Wnt signaling...
  30. Ding B, Nolan D, Butler J, James D, Babazadeh A, Rosenwaks Z, et al. Inductive angiocrine signals from sinusoidal endothelium are required for liver regeneration. Nature. 2010;468:310-5 pubmed publisher
    ..cells (LSECs) constitute a unique population of phenotypically and functionally defined VEGFR3(+)CD34(-)VEGFR2(+)VE-cadherin(+)FactorVIII(+)CD45(-) endothelial cells, which through the release of angiocrine trophogens ..
  31. Wu B, Zhang Z, Lui W, Chen X, Wang Y, Chamberlain A, et al. Endocardial cells form the coronary arteries by angiogenesis through myocardial-endocardial VEGF signaling. Cell. 2012;151:1083-96 pubmed publisher
    ..This information may help develop better cell therapies for coronary artery disease...
  32. Venkatesh D, Park K, Harrington A, Miceli Libby L, Yoon J, Liaw L. Cardiovascular and hematopoietic defects associated with Notch1 activation in embryonic Tie2-expressing populations. Circ Res. 2008;103:423-31 pubmed publisher
    ..of CD71(+)/Ter119(+) populations with an active N1ICD(+) allele and a corresponding increase in c-Kit(+)/CD71 and Flk1(+) populations, suggesting a developmental block during the transition between c-Kit- and Ter119-expressing ..
  33. Prahst C, Heroult M, Lanahan A, Uziel N, Kessler O, Shraga Heled N, et al. Neuropilin-1-VEGFR-2 complexing requires the PDZ-binding domain of neuropilin-1. J Biol Chem. 2008;283:25110-4 pubmed publisher
    ..Taken together, the experiments have identified a novel mechanism of NP-1 interaction with VEGFR-2, which involves the cytoplasmic domain of NP-1. ..
  34. Hooper A, Butler J, Nolan D, Kranz A, Iida K, Kobayashi M, et al. Engraftment and reconstitution of hematopoiesis is dependent on VEGFR2-mediated regeneration of sinusoidal endothelial cells. Cell Stem Cell. 2009;4:263-74 pubmed publisher
    ..Within the BM, VEGFR2 expression specifically demarcated a continuous network of arterioles and SECs, with arterioles uniquely ..
  35. Lugus J, Park C, Ma Y, Choi K. Both primitive and definitive blood cells are derived from Flk-1+ mesoderm. Blood. 2009;113:563-6 pubmed publisher
    ..However, this concept has not been completely proven, especially for the origin of blood cells. Using either Flk1(+/Cre);Rosa26R-EYFP or Flk1(+/Cre);Rosa26R-LacZ mice, we permanently marked Flk-1(+) cells and their progenies to ..
  36. Katz T, Singh M, Degenhardt K, RIVERA FELICIANO J, Johnson R, Epstein J, et al. Distinct compartments of the proepicardial organ give rise to coronary vascular endothelial cells. Dev Cell. 2012;22:639-50 pubmed publisher
  37. Ebos J, Lee C, Bogdanovic E, Alami J, Van Slyke P, Francia G, et al. Vascular endothelial growth factor-mediated decrease in plasma soluble vascular endothelial growth factor receptor-2 levels as a surrogate biomarker for tumor growth. Cancer Res. 2008;68:521-9 pubmed publisher
  38. Van Den Akker N, Caolo V, Wisse L, Peters P, Poelmann R, Carmeliet P, et al. Developmental coronary maturation is disturbed by aberrant cardiac vascular endothelial growth factor expression and Notch signalling. Cardiovasc Res. 2008;78:366-75 pubmed
    ..This knowledge can contribute to optimizing therapies targeting VEGF signalling by enabling balancing between angiogenesis and vascular maturation. ..
  39. Fischer C, Jonckx B, Mazzone M, Zacchigna S, Loges S, Pattarini L, et al. Anti-PlGF inhibits growth of VEGF(R)-inhibitor-resistant tumors without affecting healthy vessels. Cell. 2007;131:463-75 pubmed
    ..The efficacy and safety of alphaPlGF, its pleiotropic and complementary mechanism to VEGF(R)Is, and the negligible induction of an angiogenic rescue program suggest that alphaPlGF may constitute a novel approach for cancer treatment. ..
  40. Tammela T, Zarkada G, Wallgard E, Murtomäki A, Suchting S, Wirzenius M, et al. Blocking VEGFR-3 suppresses angiogenic sprouting and vascular network formation. Nature. 2008;454:656-60 pubmed publisher
    ..augmented VEGF-induced angiogenesis and sustained angiogenesis even in the presence of VEGFR-2 (also known as KDR or FLK-1) inhibitors, whereas antibodies against VEGFR-3 and VEGFR-2 in combination resulted in additive inhibition ..
  41. Reidy K, Villegas G, Teichman J, Veron D, Shen W, Jimenez J, et al. Semaphorin3a regulates endothelial cell number and podocyte differentiation during glomerular development. Development. 2009;136:3979-89 pubmed publisher
    ..Nephrin, WT1 and VEGFR2 were downregulated in Sema3a-overexpressing kidneys...
  42. Erskine L, Reijntjes S, Pratt T, Denti L, Schwarz Q, Vieira J, et al. VEGF signaling through neuropilin 1 guides commissural axon crossing at the optic chiasm. Neuron. 2011;70:951-65 pubmed publisher
    ..These findings have identified a permissive midline signal for axons at the chiasm midline and provide in vivo evidence that VEGF-A is an essential axon guidance cue. ..
  43. Ishijima M, Suzuki N, Hozumi K, Matsunobu T, Kosaki K, Kaneko H, et al. Perlecan modulates VEGF signaling and is essential for vascularization in endochondral bone formation. Matrix Biol. 2012;31:234-45 pubmed publisher
    ..Thus, perlecan in cartilage plays a critical role in endochondral bone formation by promoting angiogenesis essential for cartilage matrix remodeling and subsequent endochondral bone formation. ..
  44. Phng L, Potente M, Leslie J, Babbage J, Nyqvist D, Lobov I, et al. Nrarp coordinates endothelial Notch and Wnt signaling to control vessel density in angiogenesis. Dev Cell. 2009;16:70-82 pubmed publisher
    ..In vivo, loss of Nrarp, Lef1, or endothelial Ctnnb1 causes vessel regression. We suggest that the balance between Notch and Wnt signaling determines whether to make or break new vessel connections. ..
  45. Gale N, Yancopoulos G. Growth factors acting via endothelial cell-specific receptor tyrosine kinases: VEGFs, angiopoietins, and ephrins in vascular development. Genes Dev. 1999;13:1055-66 pubmed
  46. Oh J, Takahashi R, Kondo S, Mizoguchi A, Adachi E, Sasahara R, et al. The membrane-anchored MMP inhibitor RECK is a key regulator of extracellular matrix integrity and angiogenesis. Cell. 2001;107:789-800 pubmed
    ..These results support a role for RECK in the regulation of MMP-2 in vivo and implicate RECK downregulation in tumor angiogenesis. ..
  47. Zheng Y, Murakami M, Takahashi H, Yamauchi M, Kiba A, Yamaguchi S, et al. Chimeric VEGF-E(NZ7)/PlGF promotes angiogenesis via VEGFR-2 without significant enhancement of vascular permeability and inflammation. Arterioscler Thromb Vasc Biol. 2006;26:2019-26 pubmed
    ..The unique receptor binding property may shed light on VEGF-E(NZ7)/PlGF as a novel candidate for therapeutic angiogenesis. ..
  48. Schuh A, Faloon P, Hu Q, Bhimani M, Choi K. In vitro hematopoietic and endothelial potential of flk-1(-/-) embryonic stem cells and embryos. Proc Natl Acad Sci U S A. 1999;96:2159-64 pubmed
    ..Our results suggest that hematopoietic/endothelial progenitors arise independently of Flk-1, but that their subsequent migration and expansion require a Flk-1-mediated signal. ..
  49. Robert B, St John P, Abrahamson D. Direct visualization of renal vascular morphogenesis in Flk1 heterozygous mutant mice. Am J Physiol. 1998;275:F164-72 pubmed
    b>Flk1, a receptor tyrosine kinase for vascular endothelial growth factor (VEGF), is the earliest known marker for endothelial precursors (angioblasts)...
  50. Gonzalez R, Cherfils S, Escobar M, Yoo J, Carino C, Styer A, et al. Leptin signaling promotes the growth of mammary tumors and increases the expression of vascular endothelial growth factor (VEGF) and its receptor type two (VEGF-R2). J Biol Chem. 2006;281:26320-8 pubmed
    ..The inhibition of leptin signaling could serve as a potential adjuvant therapy for treatment of breast cancer and/or provide a new target for the designing strategies to prevent MT development. ..
  51. Patan S. TIE1 and TIE2 receptor tyrosine kinases inversely regulate embryonic angiogenesis by the mechanism of intussusceptive microvascular growth. Microvasc Res. 1998;56:1-21 pubmed
    ..Angiopoietin-1, a ligand that activates the TIE2 receptor, is expressed in mesenchymal cells surrounding the endothelium. This local relationship is indicative of a paracrine regulation. ..
  52. Shalaby F, Ho J, Stanford W, Fischer K, Schuh A, Schwartz L, et al. A requirement for Flk1 in primitive and definitive hematopoiesis and vasculogenesis. Cell. 1997;89:981-90 pubmed
    Mouse embryos lacking the receptor tyrosine kinase, Flk1, die without mature endothelial and hematopoietic cells...
  53. Adams R, Wilkinson G, Weiss C, Diella F, Gale N, Deutsch U, et al. Roles of ephrinB ligands and EphB receptors in cardiovascular development: demarcation of arterial/venous domains, vascular morphogenesis, and sprouting angiogenesis. Genes Dev. 1999;13:295-306 pubmed
  54. Carmeliet P, Ferreira V, Breier G, Pollefeyt S, Kieckens L, Gertsenstein M, et al. Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele. Nature. 1996;380:435-9 pubmed
  55. Tevosian S, Deconinck A, Tanaka M, Schinke M, Litovsky S, Izumo S, et al. FOG-2, a cofactor for GATA transcription factors, is essential for heart morphogenesis and development of coronary vessels from epicardium. Cell. 2000;101:729-39 pubmed
    ..Our findings provide the molecular inroad into the induction of coronary vasculature by myocardium in the developing heart. ..
  56. Lammert E, Cleaver O, Melton D. Induction of pancreatic differentiation by signals from blood vessels. Science. 2001;294:564-7 pubmed
    ..These results indicate that vessels not only provide metabolic sustenance, but also provide inductive signals for organ development. ..
  57. Lampugnani M, Orsenigo F, Gagliani M, Tacchetti C, Dejana E. Vascular endothelial cadherin controls VEGFR-2 internalization and signaling from intracellular compartments. J Cell Biol. 2006;174:593-604 pubmed
    ..Thus, VEC limits cell proliferation by retaining VEGFR-2 at the membrane and preventing its internalization into signaling compartments. ..
  58. Sakurai Y, Ohgimoto K, Kataoka Y, Yoshida N, Shibuya M. Essential role of Flk-1 (VEGF receptor 2) tyrosine residue 1173 in vasculogenesis in mice. Proc Natl Acad Sci U S A. 2005;102:1076-81 pubmed
    Flk-1 (human counterpart, KDR) tyrosine kinase, which is one of the two VEGF receptors, is crucial for vascular development...
  59. Maes C, Stockmans I, Moermans K, Van Looveren R, Smets N, Carmeliet P, et al. Soluble VEGF isoforms are essential for establishing epiphyseal vascularization and regulating chondrocyte development and survival. J Clin Invest. 2004;113:188-99 pubmed
    ..These findings indicate that the insoluble VEGF(188) isoform is insufficient for establishing epiphyseal vascularization and regulating cartilage development during endochondral bone formation...
  60. Uyttendaele H, Ho J, Rossant J, Kitajewski J. Vascular patterning defects associated with expression of activated Notch4 in embryonic endothelium. Proc Natl Acad Sci U S A. 2001;98:5643-8 pubmed
    ..of the mouse by expressing an activated form of the Notch4 protein in vasculature under the regulation of the Flk1 (VEGFR) locus...