Gene Symbol: cdh5
Description: cadherin 5
Alias: mlb, wu:fc88a07, cadherin-5, VE-cadherin (vascular epithelium), cadherin 5, type 2, VE-cadherin (vascular epithelium), fc88a07, type 2, vascular endothelial cadherin, vecdn
Species: zebrafish
Products:     cdh5

Top Publications

  1. Larson J, Wadman S, Chen E, Kerley L, Clark K, Eide M, et al. Expression of VE-cadherin in zebrafish embryos: a new tool to evaluate vascular development. Dev Dyn. 2004;231:204-13 pubmed
    ..This loss can be restored in embryos supplemented with either zebrafish or human VEGF-A, the latter indicating that genes crucial to angiogenesis have highly conserved functional activities in vertebrates. ..
  2. Herwig L, Blum Y, Krudewig A, Ellertsdottir E, Lenard A, Belting H, et al. Distinct cellular mechanisms of blood vessel fusion in the zebrafish embryo. Curr Biol. 2011;21:1942-8 pubmed publisher
    ..Here, the invaginating inner cell membrane undergoes concomitant apicobasal polarization and the vascular lumen is formed by the extension of a transcellular lumen through the EC, which forms a unicellular or seamless tube...
  3. Gore A, Lampugnani M, Dye L, Dejana E, Weinstein B. Combinatorial interaction between CCM pathway genes precipitates hemorrhagic stroke. Dis Model Mech. 2008;1:275-81 pubmed publisher
    ..These findings support the idea that minor polygenic deficits in the CCM pathway can strongly synergize to initiate ICH. ..
  4. Blum Y, Belting H, Ellertsdottir E, Herwig L, Lüders F, Affolter M. Complex cell rearrangements during intersegmental vessel sprouting and vessel fusion in the zebrafish embryo. Dev Biol. 2008;316:312-22 pubmed publisher
  5. Kim Y, Kim M, Koo T, Kim J, Koun S, Ham H, et al. Histone deacetylase is required for the activation of Wnt/?-catenin signaling crucial for heart valve formation in zebrafish embryos. Biochem Biophys Res Commun. 2012;423:140-6 pubmed publisher
    ..Taken together, our results demonstrated that HDAC activity plays a pivotal role in vertebrate heart tube formation by activating Wnt/?-catenin signaling which induces bmp4 expression in AVC myocardial cells. ..
  6. Corti P, Young S, Chen C, Patrick M, Rochon E, Pekkan K, et al. Interaction between alk1 and blood flow in the development of arteriovenous malformations. Development. 2011;138:1573-82 pubmed publisher
    ..a TGF? family type I receptor implicated in the human vascular disorder hereditary hemorrhagic telangiectasia type 2 (HHT2)...
  7. Wang Y, Kaiser M, Larson J, Nasevicius A, Clark K, Wadman S, et al. Moesin1 and Ve-cadherin are required in endothelial cells during in vivo tubulogenesis. Development. 2010;137:3119-28 pubmed publisher
    ..We suggest that Ve-cadherin and Moesin1 function to establish and maintain apical/basal polarity during multicellular lumen formation in the ISVs. ..
  8. Mitchell I, Brown T, Terada L, Amatruda J, Nwariaku F. Effect of vascular cadherin knockdown on zebrafish vasculature during development. PLoS ONE. 2010;5:e8807 pubmed publisher
    b>Vascular endothelial cadherin (VE-cad) is essential for endothelial barrier integrity and vascular sprouting. However, the role of this important protein in cardiovascular development is only recently becoming apparent...
  9. Montero Balaguer M, Swirsding K, Orsenigo F, Cotelli F, Mione M, Dejana E. Stable vascular connections and remodeling require full expression of VE-cadherin in zebrafish embryos. PLoS ONE. 2009;4:e5772 pubmed publisher
    ..This suggests that partial internalization or change of function of this protein may strongly affect vascular stability and organization. ..

More Information


  1. Sumanas S, Jorniak T, Lin S. Identification of novel vascular endothelial-specific genes by the microarray analysis of the zebrafish cloche mutants. Blood. 2005;106:534-41 pubmed
    ..Dual specificity phosphatase 5 (dusp5), cadherin 5 (cdh5; VE-cadherin), aquaporin 8 (aqp8), adrenomedullin receptor (admr), complement receptor C1qR-like (crl), ..
  2. Avraham Davidi I, Ely Y, Pham V, Castranova D, Grunspan M, Malkinson G, et al. ApoB-containing lipoproteins regulate angiogenesis by modulating expression of VEGF receptor 1. Nat Med. 2012;18:967-73 pubmed publisher
    ..These findings may open new avenues for the treatment of lipoprotein-related vascular disorders. ..
  3. Fujita M, Cha Y, Pham V, Sakurai A, Roman B, Gutkind J, et al. Assembly and patterning of the vascular network of the vertebrate hindbrain. Development. 2011;138:1705-15 pubmed publisher
    ..Knockdown of either cxcl12b or cxcr4a results in defects in basilar artery formation, showing that the assembly and patterning of this crucial artery depends on chemokine signaling. ..
  4. Bussmann J, Wolfe S, Siekmann A. Arterial-venous network formation during brain vascularization involves hemodynamic regulation of chemokine signaling. Development. 2011;138:1717-26 pubmed publisher
  5. Jin S, Herzog W, Santoro M, Mitchell T, Frantsve J, Jungblut B, et al. A transgene-assisted genetic screen identifies essential regulators of vascular development in vertebrate embryos. Dev Biol. 2007;307:29-42 pubmed
    ..The analysis of the newly defined loci should lead to a greater understanding of vascular development and possibly provide new drug targets to treat the numerous pathologies associated with dysregulated blood vessel growth. ..
  6. Nicoli S, Ribatti D, Cotelli F, Presta M. Mammalian tumor xenografts induce neovascularization in zebrafish embryos. Cancer Res. 2007;67:2927-31 pubmed
    ..These data show that the zebrafish/tumor xenograft model represents a novel tool for investigating the neovascularization process exploitable for drug discovery and gene targeting in tumor angiogenesis. ..
  7. Jin S, Beis D, Mitchell T, Chen J, Stainier D. Cellular and molecular analyses of vascular tube and lumen formation in zebrafish. Development. 2005;132:5199-209 pubmed
    ..These studies provide the tools and a cellular framework for the investigation of mutations affecting vasculogenesis in zebrafish. ..
  8. Lenard A, Ellertsdottir E, Herwig L, Krudewig A, Sauteur L, Belting H, et al. In vivo analysis reveals a highly stereotypic morphogenetic pathway of vascular anastomosis. Dev Cell. 2013;25:492-506 pubmed publisher
    ..Vascular endothelial-cadherin plays an important role early in the anastomosis process and is required for filopodial tip cell interactions and efficient formation of a single contact site. ..
  9. Sun X, Zhang R, Lin X, Xu X. Wnt3a regulates the development of cardiac neural crest cells by modulating expression of cysteine-rich intestinal protein 2 in rhombomere 6. Circ Res. 2008;102:831-9 pubmed publisher
    ..We propose that this function of wnt3a in r6 is partially mediated by crip2 expression in the premigratory cardiac NCCs, which subsequently affects cardiac function and PA patterning. ..
  10. Chen Y, Lee H, Hsu R, Chen T, Huang Y, Lo H, et al. The toxic effect of Amiodarone on valve formation in the developing heart of zebrafish embryos. Reprod Toxicol. 2012;33:233-44 pubmed publisher
    ..VE-cadherin (cdh5), normally downregulated at the endocardial cushion, was also ectopically overexpressed in the Amiodarone-treated ..
  11. Lee H, Lin Y, Lai Y, Huang W, Hu J, Tsai J, et al. Glycogen synthase kinase 3 beta in somites plays a role during the angiogenesis of zebrafish embryos. FEBS J. 2014;281:4367-83 pubmed publisher
    ..Thus, both active and inactive forms of Gsk3b mediate the cooperative signaling between Wnt/?-catenin and PI3K/AKT to control VegfAa expression in somites during angiogenesis in zebrafish embryos. ..
  12. Croushore J, Blasiole B, Riddle R, Thisse C, Thisse B, Canfield V, et al. Ptena and ptenb genes play distinct roles in zebrafish embryogenesis. Dev Dyn. 2005;234:911-21 pubmed
    ..These results indicate that ptena and ptenb encode functional enzymes and that each pten gene plays a distinct role during zebrafish embryogenesis. ..
  13. Knoll R, Postel R, Wang J, Krätzner R, Hennecke G, Vacaru A, et al. Laminin-alpha4 and integrin-linked kinase mutations cause human cardiomyopathy via simultaneous defects in cardiomyocytes and endothelial cells. Circulation. 2007;116:515-25 pubmed
  14. Craig M, Grajevskaja V, Liao H, Balciuniene J, Ekker S, Park J, et al. Etv2 and fli1b function together as key regulators of vasculogenesis and angiogenesis. Arterioscler Thromb Vasc Biol. 2015;35:865-76 pubmed publisher
    ..Etv2 alone is required for early vasculogenesis, whereas Etv2 and Fli1b function redundantly during late vasculogenesis and early embryonic angiogenesis. ..
  15. Simões F, Peterkin T, Patient R. Fgf differentially controls cross-antagonism between cardiac and haemangioblast regulators. Development. 2011;138:3235-45 pubmed publisher
    ..We propose that elevation of Fgf signalling in the anterior haemangioblast territory could have led to its recruitment into the heart field during evolution, increasing the size of the heart. ..
  16. Kurian L, Aguirre A, Sancho Martinez I, Benner C, Hishida T, Nguyen T, et al. Identification of novel long noncoding RNAs underlying vertebrate cardiovascular development. Circulation. 2015;131:1278-1290 pubmed publisher
  17. Helker C, Schuermann A, Karpanen T, Zeuschner D, Belting H, Affolter M, et al. The zebrafish common cardinal veins develop by a novel mechanism: lumen ensheathment. Development. 2013;140:2776-86 pubmed publisher
    ..that the initial delamination of the ECs as well as the directional migration within the EC sheet depend on Cadherin 5 function...
  18. Aydogan V, Lenard A, Denes A, Sauteur L, Belting H, Affolter M. Endothelial cell division in angiogenic sprouts of differing cellular architecture. Biol Open. 2015;4:1259-69 pubmed publisher
    ..Our findings illustrate that during the course of normal development, the cell division machinery can accommodate multiple tube architectures, thereby avoiding disruptions to the vascular network. ..
  19. Ulrich F, Carretero Ortega J, Menéndez J, Narvaez C, Sun B, Lancaster E, et al. Reck enables cerebrovascular development by promoting canonical Wnt signaling. Development. 2016;143:147-59 pubmed publisher
    ..Together, our findings have broad implications for both vascular and cancer biology. ..
  20. Li J, Yue Y, Zhao Q. Retinoic Acid Signaling Is Essential for Valvulogenesis by Affecting Endocardial Cushions Formation in Zebrafish Embryos. Zebrafish. 2016;13:9-18 pubmed publisher
    ..Being consistent with the reduced expression of notch1b in endocardial AVC, the VE-cadherin gene cdh5, the downstream gene of Notch signaling, was ectopically expressed in AVC of aldh1a2 morphants at 50 hpf, ..
  21. Hamm M, Kirchmaier B, Herzog W. Sema3d controls collective endothelial cell migration by distinct mechanisms via Nrp1 and PlxnD1. J Cell Biol. 2016;215:415-430 pubmed
    ..Our findings are highly relevant for understanding EC migration and the mechanisms of collective migration in other contexts. ..
  22. Wilkinson R, Koudijs M, Patient R, Ingham P, Schulte Merker S, van Eeden F. Hedgehog signaling via a calcitonin receptor-like receptor can induce arterial differentiation independently of VEGF signaling in zebrafish. Blood. 2012;120:477-88 pubmed publisher
    ..Finally, our experiments establish a dual function of Hh during induction of runx1(+) HSCs. ..
  23. Casie Chetty S, Rost M, Enriquez J, Schumacher J, Baltrunaite K, Rossi A, et al. Vegf signaling promotes vascular endothelial differentiation by modulating etv2 expression. Dev Biol. 2017;424:147-161 pubmed publisher
  24. Esser J, Charlet A, Schmidt M, Heck S, Allen A, Lother A, et al. The neuronal transcription factor NPAS4 is a strong inducer of sprouting angiogenesis and tip cell formation. Cardiovasc Res. 2017;113:222-223 pubmed publisher
    ..NPAS4 is expressed in endothelial cells, regulates VE-cadherin expression and regulates sprouting angiogenesis. ..
  25. Chen E, Larson J, Ekker S. Functional analysis of zebrafish microfibril-associated glycoprotein-1 (Magp1) in vivo reveals roles for microfibrils in vascular development and function. Blood. 2006;107:4364-74 pubmed
    ..The essential role for MAGP1 in vascular morphogenesis and function also supports a wide range of clinical applications, including therapeutic targets in vascular disease and cardiovascular tissue engineering...
  26. Bussmann J, Schulte Merker S. Rapid BAC selection for tol2-mediated transgenesis in zebrafish. Development. 2011;138:4327-32 pubmed publisher
    ..Importantly, we provide evidence that BAC size shows no apparent correlation to the transgenesis rate achieved and that there are no severe position effects. ..
  27. Donat S, Lourenço M, Paolini A, Otten C, Renz M, Abdelilah Seyfried S. Heg1 and Ccm1/2 proteins control endocardial mechanosensitivity during zebrafish valvulogenesis. elife. 2018;7: pubmed publisher
    ..Hence, the correct balance of blood-flow-dependent induction and Krit1 protein-mediated repression of klf2a and notch1b ultimately shapes cardiac valve leaflet morphology. ..
  28. Lee H, Lo H, Lo D, Su M, Hu J, Wu C, et al. Amiodarone Induces Overexpression of Similar to Versican b to Repress the EGFR/Gsk3b/Snail Signaling Axis during Cardiac Valve Formation of Zebrafish Embryos. PLoS ONE. 2015;10:e0144751 pubmed publisher
    ..A closer investigation showed that an intricate set of signaling events ultimately caused the up-regulation of cdh5. In particular, we investigated the role of EGFR signaling and the activity of Gsk3b...
  29. Chiang I, Fritzsche M, Pichol Thievend C, Neal A, Holmes K, Lagendijk A, et al. SoxF factors induce Notch1 expression via direct transcriptional regulation during early arterial development. Development. 2017;144:2629-2639 pubmed publisher
    ..These findings position SoxF transcription factors directly upstream of Notch receptor expression during the acquisition of arterial identity in vertebrates. ..
  30. Li S, Zhou X, Dang Y, Kwan Y, Chan S, Leung G, et al. Basal Flt1 tyrosine kinase activity is a positive regulator of endothelial survival and vascularization during zebrafish embryogenesis. Biochim Biophys Acta. 2015;1850:373-84 pubmed publisher
    ..The roles of Flt1 activity in endothelial cell survival in physiological vascular formation may have been previously under-appreciated. ..
  31. Zizioli D, Geumann C, Kratzke M, Mishra R, Borsani G, Finazzi D, et al. γ2 and γ1AP-1 complexes: Different essential functions and regulatory mechanisms in clathrin-dependent protein sorting. Eur J Cell Biol. 2017;96:356-368 pubmed publisher
    ..Also γ2 is essential in development. In zebrafish AP-1/γ2 and AP-1/γ1 fulfill different, essential functions in brain and the vascular system. ..
  32. Li L, Chen D, Li J, Wang X, Wang N, Xu C, et al. Aggf1 acts at the top of the genetic regulatory hierarchy in specification of hemangioblasts in zebrafish. Blood. 2014;123:501-8 pubmed publisher
    ..Knockdown of aggf1 expression decreases expression of endothelial cell-specific markers (cdh5, admr) and disrupts primitive hematopoiesis as shown by a decreased number of erythroid cells and reduced ..
  33. Sakurai T, Woolls M, Jin S, Murakami M, Simons M. Inter-cellular exchange of cellular components via VE-cadherin-dependent trans-endocytosis. PLoS ONE. 2014;9:e90736 pubmed publisher
    ..This novel form of cell-cell communications, leading to a direct exchange of cellular components, was observed in 2D and 3D-cultured endothelial cells as well as in the developing zebrafish vasculature. ..
  34. Bedell V, Yeo S, Park K, Chung J, Seth P, Shivalingappa V, et al. roundabout4 is essential for angiogenesis in vivo. Proc Natl Acad Sci U S A. 2005;102:6373-8 pubmed
    ..Also, human robo4 gene functionally compensates for loss of robo4 gene function, suggesting evolutionary conservation. This article reports an endothelial-specific function for a robo gene in vertebrates in vivo. ..
  35. Pan W, Pham V, Stratman A, Castranova D, Kamei M, Kidd K, et al. CDP-diacylglycerol synthetase-controlled phosphoinositide availability limits VEGFA signaling and vascular morphogenesis. Blood. 2012;120:489-98 pubmed publisher
    ..These results suggest that availability of CDS-controlled resynthesis of phosphoinositides is essential for angiogenesis. ..
  36. Hayashi M, Majumdar A, Li X, Adler J, Sun Z, Vertuani S, et al. VE-PTP regulates VEGFR2 activity in stalk cells to establish endothelial cell polarity and lumen formation. Nat Commun. 2013;4:1672 pubmed publisher
  37. Rissone A, Weinacht K, la Marca G, Bishop K, Giocaliere E, Jagadeesh J, et al. Reticular dysgenesis-associated AK2 protects hematopoietic stem and progenitor cell development from oxidative stress. J Exp Med. 2015;212:1185-202 pubmed publisher
    ..Our results link hematopoietic cell fate in AK2 deficiency to cellular energy depletion and increased oxidative stress. This points to the potential use of antioxidants as a supportive therapeutic modality for patients with RD. ..
  38. Fang L, Choi S, Baek J, Liu C, Almazan F, Ulrich F, et al. Control of angiogenesis by AIBP-mediated cholesterol efflux. Nature. 2013;498:118-22 pubmed publisher
    ..Our findings demonstrate that secreted AIBP positively regulates cholesterol efflux from endothelial cells and that effective cholesterol efflux is critical for proper angiogenesis...
  39. Li C, Lan Y, Schwartz Orbach L, Korol E, Tahiliani M, Evans T, et al. Overlapping Requirements for Tet2 and Tet3 in Normal Development and Hematopoietic Stem Cell Emergence. Cell Rep. 2015;12:1133-43 pubmed publisher
    ..Our results reveal essential, overlapping functions for tet genes during embryonic development and uncover a requirement for 5hmC in regulating HSC production. ..
  40. Wang Y, Pan L, Moens C, Appel B. Notch3 establishes brain vascular integrity by regulating pericyte number. Development. 2014;141:307-17 pubmed publisher
    ..These findings establish a new role for Notch signaling in brain vascular development whereby Notch3 signaling promotes expansion of the brain pericyte population. ..
  41. Bedell V, Wang Y, Campbell J, Poshusta T, Starker C, Krug R, et al. In vivo genome editing using a high-efficiency TALEN system. Nature. 2012;491:114-8 pubmed publisher
    ..We further show successful germline transmission of both EcoRV and mloxP engineered chromosomes. This combined approach offers the potential to model genetic variation as well as to generate targeted conditional alleles. ..
  42. Sauteur L, Krudewig A, Herwig L, Ehrenfeuchter N, Lenard A, Affolter M, et al. Cdh5/VE-cadherin promotes endothelial cell interface elongation via cortical actin polymerization during angiogenic sprouting. Cell Rep. 2014;9:504-13 pubmed publisher
    ..To investigate the function of Cdh5 in sprout outgrowth, we generated null mutations in the zebrafish cdh5 gene, and we found that junctional ..
  43. Aranguren X, Beerens M, Vandevelde W, Dewerchin M, Carmeliet P, Luttun A. Transcription factor COUP-TFII is indispensable for venous and lymphatic development in zebrafish and Xenopus laevis. Biochem Biophys Res Commun. 2011;410:121-6 pubmed publisher
    ..Therefore, the role of NR2F2 in EC fate determination is evolutionary conserved...
  44. Flores M, Hall C, Crosier K, Crosier P. Visualization of embryonic lymphangiogenesis advances the use of the zebrafish model for research in cancer and lymphatic pathologies. Dev Dyn. 2010;239:2128-35 pubmed publisher
    ..This work opens up a novel opportunity to further the understanding of, and potentially manipulate, human lymphangiogenesis. ..
  45. Herpers R, van de Kamp E, Duckers H, Schulte Merker S. Redundant roles for sox7 and sox18 in arteriovenous specification in zebrafish. Circ Res. 2008;102:12-5 pubmed
    ..Our study identifies members of the Sox family as key factors in specifying arteriovenous identity and will help to better understand hypotrichosis-lymphedema-telangiectasia and other diseases. ..
  46. Hultin S, Zheng Y, Mojallal M, Vertuani S, Gentili C, Balland M, et al. AmotL2 links VE-cadherin to contractile actin fibres necessary for aortic lumen expansion. Nat Commun. 2014;5:3743 pubmed publisher
    ..We propose that the VE-cadherin/amotL2 complex is responsible for transmitting mechanical force between endothelial cells for the coordination of cellular morphogenesis consistent with aortic lumen expansion and function. ..
  47. Baek Y, Lee D, So J, Kim C, Jeoung D, Lee H, et al. The tetrapeptide Arg-Leu-Tyr-Glu inhibits VEGF-induced angiogenesis. Biochem Biophys Res Commun. 2015;463:532-7 pubmed publisher
    ..Collectively, these data demonstrate that RLYE is a potent anti-angiogenic peptide that targets the VEGF signaling pathway. ..
  48. Hinits Y, Pan L, Walker C, Dowd J, Moens C, Hughes S. Zebrafish Mef2ca and Mef2cb are essential for both first and second heart field cardiomyocyte differentiation. Dev Biol. 2012;369:199-210 pubmed publisher
    ..Mef2cb single mutants have a functional heart and are viable adults. Our results show that the key role of Mef2c in myocardial differentiation is conserved throughout the vertebrate heart. ..
  49. Xie H, Ye D, Sepich D, Lin F. S1pr2/G?13 signaling regulates the migration of endocardial precursors by controlling endoderm convergence. Dev Biol. 2016;414:228-43 pubmed publisher
    ..The demonstration that endoderm convergence regulates the synchronized migration of endocardial and myocardial precursors reveals a new role of the endoderm in heart development. ..
  50. Gu W, Zhan H, Zhou X, Yao L, Yan M, Chen A, et al. MicroRNA-22 regulates inflammation and angiogenesis via targeting VE-cadherin. FEBS Lett. 2017;591:513-526 pubmed publisher
    ..Our studies demonstrate that the conserved targeting of VE-cadherin by miR-22 regulates endothelial inflammation, tissue injury, and angiogenesis. ..
  51. Sauteur L, Affolter M, Belting H. Distinct and redundant functions of Esama and VE-cadherin during vascular morphogenesis. Development. 2017;144:1554-1565 pubmed publisher
    ..We have compared the contribution of two endothelial cell-specific adhesion proteins, VE-cadherin (VE-cad/Cdh5) and Esama (endothelial cell-selective adhesion molecule a), during angiogenic sprouting and blood vessel fusion (..
  52. Nicoli S, Standley C, Walker P, Hurlstone A, Fogarty K, Lawson N. MicroRNA-mediated integration of haemodynamics and Vegf signalling during angiogenesis. Nature. 2010;464:1196-200 pubmed publisher
    ..Taken together, our work describes a novel genetic mechanism in which a microRNA facilitates integration of a physiological stimulus with growth factor signalling in endothelial cells to guide angiogenesis. ..
  53. Sumanas S, Lin S. Ets1-related protein is a key regulator of vasculogenesis in zebrafish. PLoS Biol. 2006;4:e10 pubmed
    ..These results demonstrate that Etsrp is necessary and sufficient for the initiation of vasculogenesis. ..