Genomes and Genes
Gene Symbol: Efnb2
Description: ephrin B2
Alias: ELF-2, Epl5, Eplg5, Htk-L, LERK-5, Lerk5, NLERK-1, ephrin-B2, EPH-related receptor tyrosine kinase ligand 5, HTK ligand
- Luo H, Charpentier T, Wang X, Qi S, Han B, Wu T, et al. Efnb1 and Efnb2 proteins regulate thymocyte development, peripheral T cell differentiation, and antiviral immune responses and are essential for interleukin-6 (IL-6) signaling. J Biol Chem. 2011;286:41135-52 pubmed publisher..In this study, both Efnb1 and Efnb2 were null-mutated in the T cell compartment of mice through loxP-mediated gene deletion...
- Gerety S, Anderson D. Cardiovascular ephrinB2 function is essential for embryonic angiogenesis. Development. 2002;129:1397-410 pubmed
- Dravis C, Yokoyama N, Chumley M, Cowan C, Silvany R, Shay J, et al. Bidirectional signaling mediated by ephrin-B2 and EphB2 controls urorectal development. Dev Biol. 2004;271:272-90 pubmed..Our data thus indicate that B-subclass Eph and ephrin molecules play an important role in these clinically significant midline cell-cell adhesion and fusion events. ..
- Xu N, Sun S, Gibson J, Henkemeyer M. A dual shaping mechanism for postsynaptic ephrin-B3 as a receptor that sculpts dendrites and synapses. Nat Neurosci. 2011;14:1421-9 pubmed publisher..The study thus dissects ephrin-B reverse signaling into three distinct intracellular pathways and protein-protein interactions that mediate the maturation of postsynaptic neurons. ..
- Sohl M, Lanner F, Farnebo F. Characterization of the murine Ephrin-B2 promoter. Gene. 2009;437:54-9 pubmed publisher..Mutational destruction of individual binding sites and chromatin immunoprecipitation confirmed that Meis1, MAZ and NFY physically interacted with the region and regulated promoter activity. ..
- Adams R, Diella F, Hennig S, Helmbacher F, Deutsch U, Klein R. The cytoplasmic domain of the ligand ephrinB2 is required for vascular morphogenesis but not cranial neural crest migration. Cell. 2001;104:57-69 pubmed..Our results indicate distinct requirements of functions mediated by the ephrinB carboxyterminus for developmental processes in the vertebrate embryo. ..
- Seo S, Fujita H, Nakano A, Kang M, Duarte A, Kume T. The forkhead transcription factors, Foxc1 and Foxc2, are required for arterial specification and lymphatic sprouting during vascular development. Dev Biol. 2006;294:458-70 pubmed..Taken together, our results demonstrate that Foxc transcription factors are novel regulators of arterial cell specification upstream of Notch signaling and lymphatic sprouting during embryonic development. ..
- Salvucci O, Maric D, Economopoulou M, Sakakibara S, Merlin S, Follenzi A, et al. EphrinB reverse signaling contributes to endothelial and mural cell assembly into vascular structures. Blood. 2009;114:1707-16 pubmed publisher..These results reveal a role for EphrinB signaling in orchestrating pericyte/endothelial cell assembly, and suggest that therapeutic targeting of EphrinB may prove useful for disrupting angiogenesis when it contributes to disease. ..
- Masumura T, Yamamoto K, Shimizu N, Obi S, Ando J. Shear stress increases expression of the arterial endothelial marker ephrinB2 in murine ES cells via the VEGF-Notch signaling pathways. Arterioscler Thromb Vasc Biol. 2009;29:2125-31 pubmed publisher..Exposure to shear stress induces an increase in expression of ephrinB2 in murine ES cells via VEGF-Notch signaling pathways. ..
- Zhao C, Irie N, Takada Y, Shimoda K, Miyamoto T, Nishiwaki T, et al. Bidirectional ephrinB2-EphB4 signaling controls bone homeostasis. Cell Metab. 2006;4:111-21 pubmed..Here we show that osteoclasts express the NFATc1 target gene Efnb2 (encoding ephrinB2), while osteoblasts express the receptor EphB4, along with other ephrin-Eph family members...
- Davy A, Bush J, Soriano P. Inhibition of gap junction communication at ectopic Eph/ephrin boundaries underlies craniofrontonasal syndrome. PLoS Biol. 2006;4:e315 pubmed..Our results uncover a novel role for Eph/ephrins in regulating GJC in vivo and suggest that the pleiotropic defects seen in CFNS patients are due to improper regulation of GJC in affected tissues. ..
- Egawa G, Osawa M, Uemura A, Miyachi Y, Nishikawa S. Transient expression of ephrin b2 in perinatal skin is required for maintenance of keratinocyte homeostasis. J Invest Dermatol. 2009;129:2386-95 pubmed publisher..Here, we show that ephrin B2 is transiently expressed in hair buds during embryogenesis and in dermal mesenchymal cells during the perinatal ..
- Clarke R, Yzaguirre A, Yashiro Ohtani Y, Bondue A, Blanpain C, Pear W, et al. The expression of Sox17 identifies and regulates haemogenic endothelium. Nat Cell Biol. 2013;15:502-10 pubmed publisher..Taken together, these findings position Sox17 as a key regulator of haemogenic endothelial and haematopoietic development. ..
- Fischer A, Schumacher N, Maier M, Sendtner M, Gessler M. The Notch target genes Hey1 and Hey2 are required for embryonic vascular development. Genes Dev. 2004;18:901-11 pubmed..This indicates that Hey1/Hey2 are essential transducers of Notch signals in cardiovascular development that may mediate arterial cell fate decision. ..
- Krebs L, Shutter J, Tanigaki K, Honjo T, Stark K, Gridley T. Haploinsufficient lethality and formation of arteriovenous malformations in Notch pathway mutants. Genes Dev. 2004;18:2469-73 pubmed..These results demonstrate that vascular remodeling in the mouse embryo is sensitive to Dll4 gene dosage and that Notch activation in endothelial cells is essential for embryonic vascular remodeling. ..
- Krebs L, Starling C, Chervonsky A, Gridley T. Notch1 activation in mice causes arteriovenous malformations phenocopied by ephrinB2 and EphB4 mutants. Genesis. 2010;48:146-50 pubmed publisher..Surprisingly, embryos homozygous for mutations of the ephrinB/EphB pathway genes Efnb2 and Ephb4 exhibit vascular defects and arteriovenous malformations that phenocopy the Notch1 gain of function ..
- Cowan C, Yokoyama N, Bianchi L, Henkemeyer M, Fritzsch B. EphB2 guides axons at the midline and is necessary for normal vestibular function. Neuron. 2000;26:417-30 pubmed..This suggests EphB2 may regulate ionic homeostasis and endolymph fluid production through macromolecular associations with membrane channels that transport chloride, bicarbonate, and water. ..
- Coate T, Raft S, Zhao X, Ryan A, Crenshaw E, Kelley M. Otic mesenchyme cells regulate spiral ganglion axon fasciculation through a Pou3f4/EphA4 signaling pathway. Neuron. 2012;73:49-63 pubmed publisher..Finally, Efnb2 deletion in SGNs leads to similar fasciculation defects, suggesting that ephrin-B2/EphA4 interactions are critical ..
- Wang Y, Nakayama M, Pitulescu M, Schmidt T, Bochenek M, Sakakibara A, et al. Ephrin-B2 controls VEGF-induced angiogenesis and lymphangiogenesis. Nature. 2010;465:483-6 pubmed publisher..Our results show that full VEGFR3 signalling is coupled to receptor internalization. Ephrin-B2 is a key regulator of this process and thereby controls angiogenic and lymphangiogenic growth. ..
- Iso T, Maeno T, Oike Y, Yamazaki M, Doi H, Arai M, et al. Dll4-selective Notch signaling induces ephrinB2 gene expression in endothelial cells. Biochem Biophys Res Commun. 2006;341:708-14 pubmed..Our data provide new insight into the molecular mechanism of ligand-selective Notch activation during differentiation of arterial EC. ..
- Gerety S, Wang H, Chen Z, Anderson D. Symmetrical mutant phenotypes of the receptor EphB4 and its specific transmembrane ligand ephrin-B2 in cardiovascular development. Mol Cell. 1999;4:403-14 pubmed..These data indicate that ephrin-B2-EphB4 interactions are intrinsically required in vascular endothelial cells and are consistent with the idea that they mediate bidirectional signaling essential for angiogenesis. ..
- 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. ..
- MIKO I, Henkemeyer M, Cramer K. Auditory brainstem responses are impaired in EphA4 and ephrin-B2 deficient mice. Hear Res. 2008;235:39-46 pubmed
- Bouzioukh F, Wilkinson G, Adelmann G, Frotscher M, Stein V, Klein R. Tyrosine phosphorylation sites in ephrinB2 are required for hippocampal long-term potentiation but not long-term depression. J Neurosci. 2007;27:11279-88 pubmed..Our results provide the first evidence for phosphotyrosine-dependent ephrinB reverse signaling in a neuronal network and for differential ephrinB2 reverse signaling in two forms of synaptic plasticity. ..
- 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..Blocking ephrin-B2 reverse signalling may be an attractive alternative or combinatorial anti-angiogenic therapy strategy to disrupt VEGFR2 function in tumour angiogenesis...
- Thakar S, Chenaux G, Henkemeyer M. Critical roles for EphB and ephrin-B bidirectional signalling in retinocollicular mapping. Nat Commun. 2011;2:431 pubmed publisher..These data demonstrate that both forward and reverse signalling initiated by EphB:ephrin-B interactions have a major role in dorsoventral retinal ganglion cell axon termination along the mediolateral axis of the superior colliculus. ..
- 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. ..
- 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
- Grunwald I, Korte M, Adelmann G, Plueck A, Kullander K, Adams R, et al. Hippocampal plasticity requires postsynaptic ephrinBs. Nat Neurosci. 2004;7:33-40 pubmed..This work raises the intriguing possibility that depending on the type of synapse, Eph/ephrins can be involved in activity-dependent plasticity in converse ways, with ephrinBs on the pre- or the postsynaptic side. ..
- Molotkov A, Molotkova N, Duester G. Retinoic acid guides eye morphogenetic movements via paracrine signaling but is unnecessary for retinal dorsoventral patterning. Development. 2006;133:1901-10 pubmed..or maintenance of dorsoventral patterning in the retina, as we observe normal expression of Tbx5 and ephrin B2 (Efnb2) dorsally, plus Vax2 and Ephb2 ventrally...
- Williams S, Mann F, Erskine L, Sakurai T, Wei S, Rossi D, et al. Ephrin-B2 and EphB1 mediate retinal axon divergence at the optic chiasm. Neuron. 2003;39:919-35 pubmed..EphB1 null mice exhibit a dramatically reduced ipsilateral projection, suggesting that this receptor contributes to the formation of the ipsilateral retinal projection, most likely through its repulsive interaction with ephrin-B2. ..
- You L, Lin F, Lee C, DeMayo F, Tsai M, Tsai S. Suppression of Notch signalling by the COUP-TFII transcription factor regulates vein identity. Nature. 2005;435:98-104 pubmed..1 (NP-1; also called Nrp1)--activates the Notch signalling pathway in the endothelium, causing induction of ephrin B2 expression and suppression of ephrin receptor B4 expression to establish arterial identity...
- Hayashi S, Asahara T, Masuda H, Isner J, Losordo D. Functional ephrin-B2 expression for promotive interaction between arterial and venous vessels in postnatal neovascularization. Circulation. 2005;111:2210-8 pubmed..Our study indicates that the ephrin-B2 ligand is likely to have functional expression on angiogenic arterial ECs and induce a subsequent promotive effect on venous vessels during postnatal neovascularization. ..
- Stuckmann I, Weigmann A, Shevchenko A, Mann M, Huttner W. Ephrin B1 is expressed on neuroepithelial cells in correlation with neocortical neurogenesis. J Neurosci. 2001;21:2726-37 pubmed
- Duarte A, Hirashima M, Benedito R, Trindade A, Diniz P, Bekman E, et al. Dosage-sensitive requirement for mouse Dll4 in artery development. Genes Dev. 2004;18:2474-8 pubmed..This implicates Dll4 as the specific mammalian endothelial ligand for autocrine endothelial Notch signaling, and suggests that Dll4 may be a suitable target for intervention in arterial angiogenesis. ..
- Mendes S, Henkemeyer M, Liebl D. Multiple Eph receptors and B-class ephrins regulate midline crossing of corpus callosum fibers in the developing mouse forebrain. J Neurosci. 2006;26:882-92 pubmed..Our results support a significant role for ephrins and Eph receptors in CC development and may provide insight to possible mechanisms involved in axon midline crossing and human disorder. ..
- Cowan C, Yokoyama N, Saxena A, Chumley M, Silvany R, Baker L, et al. Ephrin-B2 reverse signaling is required for axon pathfinding and cardiac valve formation but not early vascular development. Dev Biol. 2004;271:263-71 pubmed
- Raft S, Andrade L, Shao D, Akiyama H, Henkemeyer M, Wu D. Ephrin-B2 governs morphogenesis of endolymphatic sac and duct epithelia in the mouse inner ear. Dev Biol. 2014;390:51-67 pubmed publisher..Mice deficient in either the EphB2 receptor tyrosine kinase or the cognate transmembrane ligand ephrin-B2 (Efnb2) exhibit background strain-specific vestibular-behavioral dysfunction and signs of abnormal endolymph homeostasis...
- Lavine K, Long F, Choi K, Smith C, Ornitz D. Hedgehog signaling to distinct cell types differentially regulates coronary artery and vein development. Development. 2008;135:3161-71 pubmed publisher..Finally, we present evidence suggesting that coronary arteries and veins may be derived from distinct lineages. ..
- Holland S, Gale N, Mbamalu G, Yancopoulos G, Henkemeyer M, Pawson T. Bidirectional signalling through the EPH-family receptor Nuk and its transmembrane ligands. Nature. 1996;383:722-5 pubmed..Furthermore, we show that TM ligands, as well as Nuk, are phosphorylated on tyrosine in mouse embryos, indicating that this is a physiological process. EPH receptors and their TM ligands therefore mediate bidirectional cell signalling. ..
- Dravis C, Wu T, Chumley M, Yokoyama N, Wei S, Wu D, et al. EphB2 and ephrin-B2 regulate the ionic homeostasis of vestibular endolymph. Hear Res. 2007;223:93-104 pubmed
- Wang H, Chen Z, Anderson D. Molecular distinction and angiogenic interaction between embryonic arteries and veins revealed by ephrin-B2 and its receptor Eph-B4. Cell. 1998;93:741-53 pubmed..These results provide evidence that differences between arteries and veins are in part genetically determined and suggest that reciprocal signaling between these two types of vessels is crucial for morphogenesis of the capillary beds. ..
- Deng Y, Larrivee B, Zhuang Z, Atri D, Moraes F, Prahst C, et al. Endothelial RAF1/ERK activation regulates arterial morphogenesis. Blood. 2013;121:3988-96, S1-9 pubmed publisher..Our results suggest that endothelial ERK signaling is critical for both arteriogenesis and arterial-venous patterning and that RAF1 Ser(259) phosphorylation plays a critical role in preventing unopposed ERK activation. ..
- Ghori A, Freimann F, Nieminen Kelhä M, Kremenetskaia I, Gertz K, Endres M, et al. EphrinB2 Activation Enhances Vascular Repair Mechanisms and Reduces Brain Swelling After Mild Cerebral Ischemia. Arterioscler Thromb Vasc Biol. 2017;37:867-878 pubmed publisher..We also identify a novel role for ephrinB2/EphB4 signaling in the maintenance of the neurovascular homeostasis and provide a novel therapeutic approach in reducing brain swelling after stroke. ..
- Braun J, Hoffmann S, Feldner A, Ludwig T, Henning R, Hecker M, et al. Endothelial cell ephrinB2-dependent activation of monocytes in arteriosclerosis. Arterioscler Thromb Vasc Biol. 2011;31:297-305 pubmed publisher..These observations suggest a hitherto unknown link between vascular ephrinB2 expression and the proinflammatory activation of monocytes that may contribute to the pathogenesis of arteriosclerosis. ..
- Awatramani R, Soriano P, Rodriguez C, Mai J, Dymecki S. Cryptic boundaries in roof plate and choroid plexus identified by intersectional gene activation. Nat Genet. 2003;35:70-5 pubmed..Our data suggest that the roof plate and choroid plexus may be formed of functional units that are capable of differentially organizing the generation of distinct neuronal cell types at different axial levels. ..
- Pickles J. Expression of Ephs and ephrins in developing mouse inner ear. Hear Res. 2003;178:44-51 pubmed..The results suggest that the Ephs and ephrins are likely to play a part in the differentiation of the structures of the inner ear, and show which Ephs and ephrins are most likely to play important roles in the different structures. ..
- Bianchi L, Dinsio K, Davoli K, Gale N. Lac z Histochemistry and immunohistochemistry reveal ephrin-B ligand expression in the inner ear. J Histochem Cytochem. 2002;50:1641-5 pubmed..Different immunostaining patterns were found with different antibodies. Comparison with lac z expression indicated which antibody was specific for the transmembrane-bound ephrin-B2 ligand. ..
- Azizoglu D, Chong D, Villasenor A, Magenheim J, Barry D, Lee S, et al. Vascular development in the vertebrate pancreas. Dev Biol. 2016;420:67-78 pubmed publisher..This study constitutes a first-time in-depth cellular and molecular characterization of pancreatic blood vessels, as they coordinately grow along with the pancreatic epithelium. ..
- Zhang G, Brady J, Liang W, Wu Y, Henkemeyer M, Yan M. EphB4 forward signalling regulates lymphatic valve development. Nat Commun. 2015;6:6625 pubmed publisher..Furthermore, a chemical genetic approach is used to unequivocally show that the kinase activity of EphB4 is essential for lymphatic valve development. ..
- Hatch J, Mukouyama Y. Spatiotemporal mapping of vascularization and innervation in the fetal murine intestine. Dev Dyn. 2015;244:56-68 pubmed publisher..These studies provide useful anatomical data for continuing investigations on the functional mechanisms underlying intestinal organogenesis. ..
- North H, Zhao X, Kolk S, Clifford M, Ziskind D, Donoghue M. Promotion of proliferation in the developing cerebral cortex by EphA4 forward signaling. Development. 2009;136:2467-76 pubmed publisher..Furthermore, overexpression of ephrin B1 stimulated cell division of neighboring cells, supporting the hypothesis that ephrin B1-initiated forward signaling of EphA4 promotes cortical cell division. ..
- Warrier S, Nuwayhid S, Sabatino J, Sugrue K, Zohn I. Supt20 is required for development of the axial skeleton. Dev Biol. 2017;421:245-257 pubmed publisher..We demonstrate that Gcn5 and Supt20 hypomorphs show similar defects in rostral-caudal somite patterning potentially suggesting shared mechanisms. ..
- Nam J, Onitsuka I, Hatch J, Uchida Y, Ray S, Huang S, et al. Coronary veins determine the pattern of sympathetic innervation in the developing heart. Development. 2013;140:1475-85 pubmed publisher..The proposed mechanism underlies a distinct, stereotypical pattern of autonomic innervation that is adapted to the complex tissue structure and physiology of the heart. ..
- Kim Y, Hu H, Guevara Gallardo S, Lam M, Fong S, Wang R. Artery and vein size is balanced by Notch and ephrin B2/EphB4 during angiogenesis. Development. 2008;135:3755-64 pubmed publisher..Loss of ephrin B2 or its receptor EphB4 also leads to enlarged aortae and underdeveloped cardinal veins; however, endothelial ..
- Luxey M, Laussu J, Davy A. EphrinB2 sharpens lateral motor column division in the developing spinal cord. Neural Dev. 2015;10:25 pubmed publisher..First, we used a reporter mouse line to establish the spatio-temporal expression pattern of EfnB2 in the developing LMC...
- Jungas T, Perchey R, Fawal M, Callot C, Froment C, Burlet Schiltz O, et al. Eph-mediated tyrosine phosphorylation of citron kinase controls abscission. J Cell Biol. 2016;214:555-69 pubmed publisher..Our study indicates that CitK integrates intracellular and extracellular signals provided by the local environment to coordinate completion of cytokinesis. ..
- Xie Q, Yang Y, Huang J, Ninkovic J, Walcher T, Wolf L, et al. Pax6 interactions with chromatin and identification of its novel direct target genes in lens and forebrain. PLoS ONE. 2013;8:e54507 pubmed publisher..5 wild type and Pax6?/? lens placodes that suggested Efnb2, Fat4, Has2, Nav1, and Trpm3 as novel Pax6-direct targets...
- Nakajima M, Yuasa S, Ueno M, Takakura N, Koseki H, Shirasawa T. Abnormal blood vessel development in mice lacking presenilin-1. Mech Dev. 2003;120:657-67 pubmed..An in vitro assay using para-aortic splanchnopleural mesoderm (P-Sp) revealed aberrant angiogenesis in the explant culture from the mutant. These findings suggest the essential roles of PS1 in angiogenesis. ..
- Lee J, Yu Q, Shin J, Sebzda E, Bertozzi C, Chen M, et al. Klf2 is an essential regulator of vascular hemodynamic forces in vivo. Dev Cell. 2006;11:845-57 pubmed..These findings identify Klf2 as an essential hemodynamic regulator in vivo and suggest that hemodynamic regulation in response to fluid shear stress is required for cardiovascular development and function. ..