Gene Symbol: ephb4a
Description: eph receptor B4a
Alias: cb646, ephB4, rtk5, eph receptor B4a, eph-like receptor tyrosine kinase 5, ephrin type-B receptor 4 pseudogene
Species: zebrafish

Top Publications

  1. Torres Vazquez J, Gitler A, Fraser S, Berk J, Van N Pham -, Fishman M, et al. Semaphorin-plexin signaling guides patterning of the developing vasculature. Dev Cell. 2004;7:117-23 pubmed
    ..These results reveal the fundamental conservation of repulsive patterning mechanisms between axonal migration in the central nervous system and vascular endothelium during angiogenesis. ..
  2. Swift M, Pham V, Castranova D, Bell K, Poole R, Weinstein B. SoxF factors and Notch regulate nr2f2 gene expression during venous differentiation in zebrafish. Dev Biol. 2014;390:116-25 pubmed publisher
    ..We show that Notch signaling activity present in the dorsal aorta suppresses expression of nr2f2, restricting nr2f2-dependent promotion of venous differentiation to the cardinal vein. ..
  3. Leslie J, Ariza McNaughton L, Bermange A, McAdow R, Johnson S, Lewis J. Endothelial signalling by the Notch ligand Delta-like 4 restricts angiogenesis. Development. 2007;134:839-44 pubmed
    ..Thus, Dll4-Notch signalling acts as an angiogenic ;off' switch by making endothelial cells unresponsive to Vegf. ..
  4. Herbert S, Huisken J, Kim T, Feldman M, Houseman B, Wang R, et al. Arterial-venous segregation by selective cell sprouting: an alternative mode of blood vessel formation. Science. 2009;326:294-8 pubmed publisher
    ..These processes were regulated by the ligand EphrinB2 and its receptor EphB4, which are expressed in arterial-fated and venous-fated progenitors, respectively, and interact to orient the ..
  5. 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...
  6. Cermenati S, Moleri S, Cimbro S, Corti P, Del Giacco L, Amodeo R, et al. Sox18 and Sox7 play redundant roles in vascular development. Blood. 2008;111:2657-66 pubmed
    ..Our data suggest that a defect in arteriovenous identity could be responsible for the formation of telangiectases in patients with HLT. ..
  7. Kida Y, Sato T, Miyasaka K, Suto A, Ogura T. Daam1 regulates the endocytosis of EphB during the convergent extension of the zebrafish notochord. Proc Natl Acad Sci U S A. 2007;104:6708-13 pubmed
    ..We elucidate the molecular mechanism underlying the CE movement of notochord cells with Daam1 as a dynamic coordinator of endocytosis and cytoskeletal remodeling. ..
  8. 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. ..
  9. Hu Z, Liu Y, Huarng M, Menegatti M, Reyon D, Rost M, et al. Genome editing of factor X in zebrafish reveals unexpected tolerance of severe defects in the common pathway. Blood. 2017;130:666-676 pubmed publisher
    ..Further study as to how fish tolerate what is an early lethal mutation in mammals could facilitate improvement of diagnostics and therapeutics for affected patients with bleeding disorders. ..

More Information


  1. Kohli V, Schumacher J, Desai S, Rehn K, Sumanas S. Arterial and venous progenitors of the major axial vessels originate at distinct locations. Dev Cell. 2013;25:196-206 pubmed publisher
    ..We propose a revised model of arterial-venous differentiation that explains how angioblasts choose between an arterial and venous fate. ..
  2. Yu P, Gu S, Bu J, Du J. TRPC1 is essential for in vivo angiogenesis in zebrafish. Circ Res. 2010;106:1221-32 pubmed publisher
    ..It implicates that TRPC1 may represent a potential target for treating pathological angiogenesis. ..
  3. 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. ..
  4. Qian L, Wang Y, Jiang Q, Zhong T, Song H. Ethanol disrupts the formation of hypochord and dorsal aorta during the development of embryonic zebrafish. Sci China C Life Sci. 2005;48:608-15 pubmed
    ..histological sections, the in situ hybridization experiments with arterial and venous biomarkers (ephrinB2, ephB4) suggested that ethanol mainly interrupts the development of dorsal aorta while has little effect on axial vein...
  5. Du J, Yang Q, Luo L, Yang D. C1qr and C1qrl redundantly regulate angiogenesis in zebrafish through controlling endothelial Cdh5. Biochem Biophys Res Commun. 2017;483:482-487 pubmed publisher
    ..These data demonstrate that c1qr and c1qrl redundantly regulate angiogenesis through controlling the expression of the endothelial junctional molecule Cdh5, thus playing an important role in angiogenesis. ..
  6. Ren C, Wang L, Jia X, Liu Y, Dong Z, Jin Y, et al. Activated N-Ras signaling regulates arterial-venous specification in zebrafish. J Hematol Oncol. 2013;6:34 pubmed publisher
  7. Jang I, Lu Y, Zhao L, Wenzel P, Kume T, Datta S, et al. Notch1 acts via Foxc2 to promote definitive hematopoiesis via effects on hemogenic endothelium. Blood. 2015;125:1418-26 pubmed publisher
    ..These data establish a pathway linking Notch signaling to Foxc2 in hemogenic endothelial cells to promote definitive hematopoiesis. ..
  8. Nicoli S, Tobia C, Gualandi L, De Sena G, Presta M. Calcitonin receptor-like receptor guides arterial differentiation in zebrafish. Blood. 2008;111:4965-72 pubmed publisher
    ..These data demonstrate that crlr plays a nonredundant role in arterial differentiation, representing a novel element of the sonic hedgehog-vegf-notch signaling cascade that controls arterial/venous fate. ..
  9. Li W, Chen J, Deng M, Jing Q. The zebrafish Tie2 signaling controls tip cell behaviors and acts synergistically with Vegf pathway in developmental angiogenesis. Acta Biochim Biophys Sin (Shanghai). 2014;46:641-6 pubmed publisher
    ..These observations demonstrate that Tie2 is an important regulator of tip cell behaviors. Moreover, these findings provide in vivo evidence that Tie2 acts coordinately with Vegf signaling to control angiogenesis. ..
  10. Cooke J, Xu Q, Wilson S, Holder N. Characterisation of five novel zebrafish Eph-related receptor tyrosine kinases suggests roles in patterning the neural plate. Dev Genes Evol. 1997;206:515-531 pubmed
    ..Here we report the identification of five new zebrafish Eph-related RTKs (rtk4, rtk5, rtk6, rtk7 and rtk8) and describe their dynamic expression patterns...
  11. Hirashima M, Suda T. Differentiation of arterial and venous endothelial cells and vascular morphogenesis. Endothelium. 2006;13:137-45 pubmed
    ..These insights indicate that the balance of these genetic factors and modification by epigenetic factors such as hemodynamics and oxygen tension are important for proper endothelial cell identities in vascular morphogenesis. ..
  12. Tobia C, Chiodelli P, Nicoli S, Dell Era P, Buraschi S, Mitola S, et al. Sphingosine-1-phosphate receptor-1 controls venous endothelial barrier integrity in zebrafish. Arterioscler Thromb Vasc Biol. 2012;32:e104-16 pubmed publisher
    ..morphants are characterized by downregulation of vascular endothelial cadherin (VE-cadherin) and Eph receptor EphB4a expression and by disorganization of zonula occludens 1 junctions in posterior cardinal vein endothelium, with no ..
  13. Huang H, Jin T, Wang L, Wang F, Zhang R, Pan Y, et al. The RAS guanyl nucleotide-releasing protein RasGRP1 is involved in lymphatic development in zebrafish. J Biol Chem. 2013;288:2355-64 pubmed publisher
    ..Taken together, this finding demonstrates a critical role for RasGRP1 in lymphatic development in zebrafish. ..
  14. Chen D, Li L, Tu X, Yin Z, Wang Q. Functional characterization of Klippel-Trenaunay syndrome gene AGGF1 identifies a novel angiogenic signaling pathway for specification of vein differentiation and angiogenesis during embryogenesis. Hum Mol Genet. 2013;22:963-76 pubmed publisher
    ..g. notch5). Knockdown of AGGF1 expression resulted in a loss of venous identity (loss of expression of flt4, ephb4 and dab2), but had no effect on the expression of arterial development...
  15. Mouillesseaux K, Chen J. Mutation in utp15 disrupts vascular patterning in a p53-dependent manner in zebrafish embryos. PLoS ONE. 2011;6:e25013 pubmed publisher
    ..Taken together, our data demonstrate an early embryonic effect of Utp15 deficiency on cell survival and the normal patterning of the vasculature and highlight an anti-angiogenic role of p53 in developing embryos. ..
  16. Rodriguez F, Vacaru A, Overvoorde J, den Hertog J. The receptor protein-tyrosine phosphatase, Dep1, acts in arterial/venous cell fate decisions in zebrafish development. Dev Biol. 2008;324:122-30 pubmed publisher
    ..Our results suggest a model in which Dep1 acts upstream in a signaling pathway inhibiting PI3K, resulting in expression of Notch and Grl, thus regulating arterial specification in development. ..
  17. Cooke J, Moens C, Roth L, Durbin L, Shiomi K, Brennan C, et al. Eph signalling functions downstream of Val to regulate cell sorting and boundary formation in the caudal hindbrain. Development. 2001;128:571-80 pubmed
    ..Indeed, expression of the receptor ephB4a coincides with val in r5/6, whilst ephrin-B2a, which encodes a ligand for EphB4a, is expressed in r4 and r7, ..
  18. Choe C, Crump J. Eph-Pak2a signaling regulates branching of the pharyngeal endoderm by inhibiting late-stage epithelial dynamics. Development. 2015;142:1089-94 pubmed publisher
    ..Here, we report novel requirements for the EphrinB ligands B2a and B3b, the Ephb4a receptor and the Pak2a kinase in the development of pouches and the posterior facial skeleton that depends on ..
  19. Chen E, Hermanson S, Ekker S. Syndecan-2 is essential for angiogenic sprouting during zebrafish development. Blood. 2004;103:1710-9 pubmed
    ..Syndecan-2 as a novel angiogenic factor is a potential candidate for use in the development of angiogenesis-based therapies. ..
  20. Zygmunt T, Gay C, Blondelle J, Singh M, Flaherty K, Means P, et al. Semaphorin-PlexinD1 signaling limits angiogenic potential via the VEGF decoy receptor sFlt1. Dev Cell. 2011;21:301-14 pubmed publisher
    ..Hence, Sema-PlxnD1 signaling regulates distinct but related aspects of angiogenesis: the spatial allocation of angiogenic capacity within a primary vessel and sprout guidance. ..
  21. 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
  22. Schmitt C, Woolls M, Jin S. Mutant-specific gene expression profiling identifies SRY-related HMG box 11b (SOX11b) as a novel regulator of vascular development in zebrafish. Mol Cells. 2013;35:166-72 pubmed publisher
    ..Taken together, our analyses illustrate a complex regulation of endothelial specification and differentiation during vertebrate development. ..
  23. Wu B, Chiu C, Chen C, Wang W, Wang J, Wen Z, et al. Nuclear receptor subfamily 2 group F member 1a (nr2f1a) is required for vascular development in zebrafish. PLoS ONE. 2014;9:e105939 pubmed publisher
    ..We further showed that nr2f1a likely interact with Notch signaling by examining nr2f1a expression in rbpsuh morphants and DAPT-treatment embryos. Together, we show nr2f1a plays a critical role for vascular development in zebrafish. ..
  24. Lamont R, Wu C, Ryu J, Vu W, Davari P, Sobering R, et al. The LIM-homeodomain transcription factor Islet2a promotes angioblast migration. Dev Biol. 2016;414:181-92 pubmed publisher
    ..Thus Isl2a may act as an intermediate between Notch signaling and genetic programs controlling angioblast number and migration, placing it as a novel transcriptional regulator of early angiogenesis. ..
  25. Zhang J, Jiang Z, Liu X, Meng A. Eph/ephrin signaling maintains the boundary of dorsal forerunner cell cluster during morphogenesis of the zebrafish embryonic left-right organizer. Development. 2016;143:2603-15 pubmed publisher
    ..Therefore, our data uncover an important role of Eph/ephrin signaling in maintaining DFC cluster boundary and KV boundary for normal left-right asymmetrical development. ..
  26. Kawasaki J, Aegerter S, Fevurly R, Mammoto A, Mammoto T, Sahin M, et al. RASA1 functions in EPHB4 signaling pathway to suppress endothelial mTORC1 activity. J Clin Invest. 2014;124:2774-84 pubmed publisher
    ..we tested the hypothesis that RASA1 performs a critical effector function downstream of the endothelial receptor EPHB4. In zebrafish models, we found that either RASA1 or EPHB4 deficiency induced strikingly similar abnormalities in ..
  27. Hermans K, Claes F, Vandevelde W, Zheng W, Geudens I, Orsenigo F, et al. Role of synectin in lymphatic development in zebrafish and frogs. Blood. 2010;116:3356-66 pubmed publisher
    ..These findings reveal a novel role for synectin in lymphatic development...
  28. Minehata K, Kawahara A, Suzuki T. meis1 regulates the development of endothelial cells in zebrafish. Biochem Biophys Res Commun. 2008;374:647-52 pubmed publisher
    ..Thus, these results implicate that meis1 is a novel regulator involved in endothelial cell development, presumably affecting the vegf signaling pathway. ..
  29. Sato T, Hamaoka T, Aizawa H, Hosoya T, Okamoto H. Genetic single-cell mosaic analysis implicates ephrinB2 reverse signaling in projections from the posterior tectum to the hindbrain in zebrafish. J Neurosci. 2007;27:5271-9 pubmed
    ..These results may provide a neuroanatomical and molecular basis for the motor command map in the tectum. ..
  30. Hernandez R, Rikhof H, Bachmann R, Moens C. vhnf1 integrates global RA patterning and local FGF signals to direct posterior hindbrain development in zebrafish. Development. 2004;131:4511-20 pubmed
    ..The different requirements for vhnf1 and val to repress hoxb1a and ephrin-B2a, respectively, demonstrate that not all aspects of an individual rhombomere's identity are regulated coordinately. ..