Genomes and Genes
Gene Symbol: Efna2
Description: ephrin A2
Alias: CEK7L, Elf1, Epl6, Eplg6, Lerk6, ephrin-A2, CEK7-ligand, EPH related receptor tyrosine kinase ligand 6, ephrin A6
- Basson M, Echevarria D, Ahn C, Sudarov A, Joyner A, Mason I, et al. Specific regions within the embryonic midbrain and cerebellum require different levels of FGF signaling during development. Development. 2008;135:889-98 pubmed publisher..We suggest a molecular explanation for this phenomenon by providing evidence that FGF signaling functions to inhibit the BMP signaling that promotes roof plate development. ..
- 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. ..
- North H, Karim A, Jacquin M, Donoghue M. EphA4 is necessary for spatially selective peripheral somatosensory topography. Dev Dyn. 2010;239:630-8 pubmed publisher..EphA4's selective effect on a subset of whiskers implicates cell-based signaling in the establishment of position-dependent connectivity and topography in the peripheral somatosensory system. ..
- Cerretti D, Nelson N. Characterization of the genes for mouse LERK-3/Ephrin-A3 (Epl3), mouse LERK-4/Ephrin-A4 (Epl4), and human LERK-6/Ephrin-A2 (EPLG6): conservation of intron/exon structure. Genomics. 1998;47:131-5 pubmed..receptor family ligands mouse LERK-3/Ephrin-A3 (Epl3), mouse LERK-4/Ephrin-A4 (Epl4), and human LERK-6/Ephrin-A2 (EPLG6)...
- Saeger B, Suhm M, Neubüser A. Ephrin/ephrin receptor expression during early stages of mouse inner ear development. Dev Dyn. 2011;240:1578-85 pubmed publisher..5 and E10, and report their detailed expression patterns. Our results reveal dynamic expression of several members of the ephrin/Eph family consistent with functions in otic placode development, invagination and neuroblast delamination. ..
- van Eyll J, Passante L, Pierreux C, Lemaigre F, Vanderhaeghen P, Rousseau G. Eph receptors and their ephrin ligands are expressed in developing mouse pancreas. Gene Expr Patterns. 2006;6:353-9 pubmed..We conclude that specific members of the Eph/ephrin family are expressed in embryonic pancreas according to a dynamic temporal and regional pattern. ..
- Abdul Latif M, Salazar J, Marshak S, Dinh M, Cramer K. Ephrin-A2 and ephrin-A5 guide contralateral targeting but not topographic mapping of ventral cochlear nucleus axons. Neural Dev. 2015;10:27 pubmed publisher..These classes may rely in part on common signaling pathways. ..
- Lyckman A, Jhaveri S, Feldheim D, Vanderhaeghen P, Flanagan J, Sur M. Enhanced plasticity of retinothalamic projections in an ephrin-A2/A5 double mutant. J Neurosci. 2001;21:7684-90 pubmed..The present findings thus show that the targeting of retinothalamic projections can be surgically manipulated in the mouse and that such plasticity can be controlled by proteins known to regulate topographic mapping. ..
- Gatto G, Morales D, Kania A, Klein R. EphA4 receptor shedding regulates spinal motor axon guidance. Curr Biol. 2014;24:2355-65 pubmed publisher..Our study reveals a novel mechanism to regulate guidance decision at an intermediate target based on the modulation of ligand availability by the proteolytic processing of the receptor. ..
- Rajagopalan S, Deitinghoff L, Davis D, Conrad S, Skutella T, Chedotal A, et al. Neogenin mediates the action of repulsive guidance molecule. Nat Cell Biol. 2004;6:756-62 pubmed..Dorsal root ganglion axons are unresponsive to RGM but are converted to a responsive state by neogenin expression. Thus, neogenin functions as an RGM receptor. ..
- Yates N, Robertson D, Martin Iverson M, Rodger J. Auditory brainstem responses of ephrin-A2, ephrin-A5(-/-) and ephrin-A2A5(-/-) mice. Audiol Neurootol. 2014;19:115-26 pubmed publisher..There were also alterations in ABR wave peak amplitudes that were specific to each mouse strain which suggested both peripheral and central involvement of EphA-ephrin-A signalling in auditory function. ..
- Zhu R, Cho K, Chen D, Yang L. Ephrin-A2 and -A3 are negative regulators of the regenerative potential of MÃ¶ller cells. Chin Med J (Engl). 2014;127:3438-42 pubmed..Manipulating ephrin-A signaling may thus represent a novel strategy for stimulating neuroregeneration from endogenous progenitors to participate in retinal repair in case of disease or damage. ..
- Yue Y, Chen Z, Gale N, Blair Flynn J, Hu T, Yue X, et al. Mistargeting hippocampal axons by expression of a truncated Eph receptor. Proc Natl Acad Sci U S A. 2002;99:10777-82 pubmed..Our observations provide strong support for a critical role of Eph family guidance factors in regulating ontogeny of hippocampal projections. ..
- Shao H, Lou L, Pandey A, Verderame M, Siever D, Dixit V. cDNA cloning and characterization of a Cek7 receptor protein-tyrosine kinase ligand that is identical to the ligand (ELF-1) for the Mek-4 and Sek receptor protein-tyrosine kinases. J Biol Chem. 1995;270:3467-70 pubmed..The Cek7 ligand shows a 48% sequence identity at the protein level to B61, a ligand for the related Eck RPTK, 30% to the Cek5 ..
- Giannoni E, Taddei M, Parri M, Bianchini F, Santosuosso M, Grifantini R, et al. EphA2-mediated mesenchymal-amoeboid transition induced by endothelial progenitor cells enhances metastatic spread due to cancer-associated fibroblasts. J Mol Med (Berl). 2013;91:103-15 pubmed publisher..We therefore underscore that the metastatic advantage given by tumor microenvironment embraces different motility strategies and propose EphA2-targeted tools as useful adjuvants in anti-metastatic treatments. ..
- Luukko K, Løes S, Kvinnsland I, Kettunen P. Expression of ephrin-A ligands and EphA receptors in the developing mouse tooth and its supporting tissues. Cell Tissue Res. 2005;319:143-52 pubmed..These results suggest regulatory roles for ephrin-A/EphA signaling in the formation of the tooth organ proper and its supporting tissues. ..
- Wurzman R, Forcelli P, Griffey C, Kromer L. Repetitive grooming and sensorimotor abnormalities in an ephrin-A knockout model for Autism Spectrum Disorders. Behav Brain Res. 2015;278:115-28 pubmed publisher..We therefore conclude that ephrin-A2/-A3 DKO mice have utility as a novel ASD model with an emphasis on sensory abnormalities and restricted, repetitive behavioral symptoms. ..
- Suda Y, Hossain Z, Kobayashi C, Hatano O, Yoshida M, Matsuo I, et al. Emx2 directs the development of diencephalon in cooperation with Otx2. Development. 2001;128:2433-50 pubmed..Consequently, development of the dorsal and ventral thalamus and anterior pretectum requires cooperation between Emx2 and Otx2, whereas Emx2 expression is incompatible with development of the commissural region of the pretectum. ..
- Hattori M, Osterfield M, Flanagan J. Regulated cleavage of a contact-mediated axon repellent. Science. 2000;289:1360-5 pubmed..These studies reveal mechanisms for protease recognition and control of cell surface proteins, and, for ephrin-A2, they may provide a means for efficient axon detachment and termination of signaling. ..
- Thompson J, Zembrzycki A, Mansouri A, Ziman M. Pax7 is requisite for maintenance of a subpopulation of superior collicular neurons and shows a diverging expression pattern to Pax3 during superior collicular development. BMC Dev Biol. 2008;8:62 pubmed publisher..The differential nature of Pax7 and Pax3 with respect to neuronal differentiation may have implications for future stem cell therapies aimed at exploiting their developmental capabilities. ..
- Ciossek T, Ullrich A. Identification of Elf-1 and B61 as high affinity ligands for the receptor tyrosine kinase MDK1. Oncogene. 1997;14:35-43 pubmed..These findings implicate MDK1 in patterning processes during early mouse embryogenesis and suggest MDK1 involvement in early organogenesis and midbrain development. ..
- 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. ..
- Yu X, Wang G, Gilmore A, Yee A, Li X, Xu T, et al. Accelerated experience-dependent pruning of cortical synapses in ephrin-A2 knockout mice. Neuron. 2013;80:64-71 pubmed publisher..Together, our results suggest that ephrin-A2 regulates experience-dependent, NMDA receptor-mediated synaptic pruning through glial glutamate transport during maturation of the mouse cortex. ..
- Gale N, Holland S, Valenzuela D, Flenniken A, Pan L, Ryan T, et al. Eph receptors and ligands comprise two major specificity subclasses and are reciprocally compartmentalized during embryogenesis. Neuron. 1996;17:9-19 pubmed..This reciprocal compartmentalization implicates the Eph family in the formation of spatial boundaries that may help to organize the developing body plan. ..
- Rogers J, Ciossek T, Menzel P, Pasquale E. Eph receptors and ephrins demarcate cerebellar lobules before and during their formation. Mech Dev. 1999;87:119-28 pubmed..These expression patterns define previously unknown developmental units and suggest that Eph family proteins may contribute to cerebellar morphogenesis. ..
- Steinecke A, Gampe C, Zimmer G, Rudolph J, Bolz J. EphA/ephrin A reverse signaling promotes the migration of cortical interneurons from the medial ganglionic eminence. Development. 2014;141:460-71 pubmed publisher..reverse signaling in MGE-derived interneurons promotes their migration and that this effect is mediated by ephrin A2 ligands...
- Holmberg J, Armulik A, Senti K, Edoff K, Spalding K, Momma S, et al. Ephrin-A2 reverse signaling negatively regulates neural progenitor proliferation and neurogenesis. Genes Dev. 2005;19:462-71 pubmed..The identification of ephrin-A2 and EphA7 as negative regulators of progenitor cell proliferation reveals a novel mechanism to control cell numbers in the brain. ..
- Merrill A, Bochukova E, Brugger S, Ishii M, Pilz D, Wall S, et al. Cell mixing at a neural crest-mesoderm boundary and deficient ephrin-Eph signaling in the pathogenesis of craniosynostosis. Hum Mol Genet. 2006;15:1319-28 pubmed..This provides genetic evidence that Twist1, Msx2 and Efna4 function together in boundary formation and the pathogenesis of coronal synostosis...
- Xavier G, Miletich I, Cobourne M. Ephrin Ligands and Eph Receptors Show Regionally Restricted Expression in the Developing Palate and Tongue. Front Physiol. 2016;7:60 pubmed publisher..These results suggest regulatory roles for ephrin-EphA signaling in development of the murine palate and tongue. ..
- Lee S, Danielian P, Fritzsch B, McMahon A. Evidence that FGF8 signalling from the midbrain-hindbrain junction regulates growth and polarity in the developing midbrain. Development. 1997;124:959-69 pubmed..Taken together our results suggest that FGF8 signalling from the isthmus has a key role in coordinately regulating growth and polarity in the developing mesencephalon. ..
- Garel S, Yun K, Grosschedl R, Rubenstein J. The early topography of thalamocortical projections is shifted in Ebf1 and Dlx1/2 mutant mice. Development. 2002;129:5621-34 pubmed..These observations suggest that the topography of thalamocortical projections is not strictly determined by cues located within the neocortex and may be regulated by the relative positioning of thalamic axons inside the basal ganglia. ..
- Jiao J, Feldheim D, Chen D. Ephrins as negative regulators of adult neurogenesis in diverse regions of the central nervous system. Proc Natl Acad Sci U S A. 2008;105:8778-83 pubmed publisher..These findings suggest that neural cell replacement therapies for neurodegeneration or injury in the adult CNS may be achieved by manipulating ephrin signaling pathways. ..
- Ellsworth C, Lyckman A, Feldheim D, Flanagan J, Sur M. Ephrin-A2 and -A5 influence patterning of normal and novel retinal projections to the thalamus: conserved mapping mechanisms in visual and auditory thalamic targets. J Comp Neurol. 2005;488:140-51 pubmed..Furthermore, when mapping labels and other cues are expressed in multiple target zones, novel projections are patterned according to rules that operate in their canonical targets. ..
- Aoki M, Yamashita T, Tohyama M. EphA receptors direct the differentiation of mammalian neural precursor cells through a mitogen-activated protein kinase-dependent pathway. J Biol Chem. 2004;279:32643-50 pubmed..Our results identify EphA receptors as positive regulators of the mitogen-activated protein kinase pathway that exerts neurogenesis of neural precursor cells from the developing central nervous system. ..
- Aasheim H, Pedeutour F, Grosgeorge J, Logtenberg T. Cloning, chromosal mapping, and tissue expression of the gene encoding the human Eph-family kinase ligand ephrin-A2. Biochem Biophys Res Commun. 1998;252:378-82 pubmed..Using PCR-based screening of genomic DNA from human x rodent hybrid cell lines, the gene encoding ephrin-A2 (EFNA2) was assigned to chromosome 19...
- Park S, Sanchez M. The Eek receptor, a member of the Eph family of tyrosine protein kinases, can be activated by three different Eph family ligands. Oncogene. 1997;14:533-42 pubmed..These findings suggest that Eek receptor can be activated by at least three different GPI-linked ligands. ..
- Yates N, Martin Iverson M, Rodger J. The role of ephrin-A2 and ephrin-A5 in sensorimotor control and gating. Behav Brain Res. 2014;275:225-33 pubmed publisher..We propose that majority of the changes observed ephrin-A2 and ephrin-A5 KO mice appear to be mediated by the effects on motor neurons and their muscle targets, rather than changes in auditory sensitivity. ..
- Shao H, Lou L, Pandey A, Pasquale E, Dixit V. cDNA cloning and characterization of a ligand for the Cek5 receptor protein-tyrosine kinase. J Biol Chem. 1994;269:26606-9 pubmed..The expressed Cek5 ligand is functionally active as it induces autophosphorylation of the Cek5 RPTK. ..
- Yue Y, Su J, Cerretti D, Fox G, Jing S, Zhou R. Selective inhibition of spinal cord neurite outgrowth and cell survival by the Eph family ligand ephrin-A5. J Neurosci. 1999;19:10026-35 pubmed
- Fujii H, Tatsumi K, Kosaka K, Yoshioka S, Fujiwara H, Fujii S. Eph-ephrin A system regulates murine blastocyst attachment and spreading. Dev Dyn. 2006;235:3250-8 pubmed..These findings suggest an important role of the Eph-ephrin A system in regulating the initial embryo-maternal contact during the cross-talk period that precedes embryo implantation. ..
- Wang L, Klein R, Zheng B, Marquardt T. Anatomical coupling of sensory and motor nerve trajectory via axon tracking. Neuron. 2011;71:263-77 pubmed publisher..Assembly of peripheral nerve pathways thus involves motor axon subtype-specific signals that couple sensory projections to discrete motor pathways. ..
- Hjorth J, Sterratt D, Cutts C, Willshaw D, Eglen S. Quantitative assessment of computational models for retinotopic map formation. Dev Neurobiol. 2015;75:641-66 pubmed publisher..Our article demonstrates the importance of testing retinotopic models against as full a range of phenotypes as possible, and we have made available MATLAB software, we wrote to facilitate this process. ..
- Wang Y, Ni Z, Zhou C. Denervation-induced spatiotemporal upregulation of ephrin-A2 in the mouse hippocampus after transections of the perforant path. FEBS Lett. 2005;579:1055-60 pubmed..In addition, ephrin-A2 expression was observed in synapses during reactive synaptogenesis, suggesting that this molecule might also be implicated in the formation and maturation of synapses in the denervated areas. ..
- Homman Ludiye J, Kwan W, de Souza M, Rodger J, Bourne J. Ephrin-A2 regulates excitatory neuron differentiation and interneuron migration in the developing neocortex. Sci Rep. 2017;7:11813 pubmed publisher..The disturbance to the architecture of the neocortex observed following deletion of ephrin-A2 signaling shares many similarities with defects found in the neocortex of children diagnosed with autism spectrum disorder. ..
- Flenniken A, Gale N, Yancopoulos G, Wilkinson D. Distinct and overlapping expression patterns of ligands for Eph-related receptor tyrosine kinases during mouse embryogenesis. Dev Biol. 1996;179:382-401 pubmed
- Naruse Nakajima C, Asano M, Iwakura Y. Involvement of EphA2 in the formation of the tail notochord via interaction with ephrinA1. Mech Dev. 2001;102:95-105 pubmed..These observations suggest that EphA2 and its ligands are involved in the positioning of the tail notochord through repulsive signals between cells expressing these molecules on the surface. ..
- Yun M, Johnson R, Antic A, Donoghue M. EphA family gene expression in the developing mouse neocortex: regional patterns reveal intrinsic programs and extrinsic influence. J Comp Neurol. 2003;456:203-16 pubmed
- Tanaka M, Ohashi R, Nakamura R, Shinmura K, Kamo T, Sakai R, et al. Tiam1 mediates neurite outgrowth induced by ephrin-B1 and EphA2. EMBO J. 2004;23:1075-88 pubmed..These results indicate that Tiam1 is required for neurite outgrowth induced by both ephrin-B1-mediated reverse signaling and EphA2-mediated forward signaling. ..
- Depaepe V, Suarez Gonzalez N, Dufour A, Passante L, Gorski J, Jones K, et al. Ephrin signalling controls brain size by regulating apoptosis of neural progenitors. Nature. 2005;435:1244-50 pubmed..Together, these results identify ephrin/Eph signalling as a physiological trigger for apoptosis that can alter brain size and shape by regulating the number of neural progenitors. ..
- Funk S, Yurdagul A, Albert P, Traylor J, Jin L, Chen J, et al. EphA2 activation promotes the endothelial cell inflammatory response: a potential role in atherosclerosis. Arterioscler Thromb Vasc Biol. 2012;32:686-95 pubmed publisher..Coupled with EphA2 expression in mouse and human atherosclerotic plaques, these data implicate EphA2 as a novel proinflammatory mediator and potential regulator of atherosclerotic plaque development. ..
- Cheng H, Flanagan J. Identification and cloning of ELF-1, a developmentally expressed ligand for the Mek4 and Sek receptor tyrosine kinases. Cell. 1994;79:157-68 pubmed..Its sequence is homologous with B61, a ligand for the Eck kinase, defining a family of related ligands. The expression domains of ELF-1, Mek4 and Sek indicate potential roles in embryonic patterning. ..
- Knoll B, Zarbalis K, Wurst W, Drescher U. A role for the EphA family in the topographic targeting of vomeronasal axons. Development. 2001;128:895-906 pubmed..In summary, these data, which are derived from in vitro and in vivo experiments, indicate an important role of the EphA family in setting up the vomeronasal projection. ..
- Islam S, Loizides A, Fialkovich J, Grand R, Montgomery R. Developmental expression of Eph and ephrin family genes in mammalian small intestine. Dig Dis Sci. 2010;55:2478-88 pubmed publisher..Continued intestinal expression of other family members implicates a role in differentiation. ..
- Toth J, Cutforth T, Gelinas A, Bethoney K, Bard J, Harrison C. Crystal structure of an ephrin ectodomain. Dev Cell. 2001;1:83-92 pubmed..The high sequence similarity among ephrin ectodomains indicates that all ephrins may be modeled upon the ephrin-B2 structure presented here. ..
- Cang J, Kaneko M, Yamada J, Woods G, Stryker M, Feldheim D. Ephrin-as guide the formation of functional maps in the visual cortex. Neuron. 2005;48:577-89 pubmed..Together with earlier work on the retinogeniculate map, the current findings show that the same molecular interactions may operate at successive stages of the visual pathway to organize maps. ..
- Pfeiffenberger C, Cutforth T, Woods G, Yamada J, RENTERIA R, Copenhagen D, et al. Ephrin-As and neural activity are required for eye-specific patterning during retinogeniculate mapping. Nat Neurosci. 2005;8:1022-7 pubmed..Thus, ephrin-As and neural activity act together to control patterning of eye-specific retinogeniculate layers. ..
- Chadaram S, LASKOWSKI M, Madison R. Topographic specificity within membranes of a single muscle detected in vitro. J Neurosci. 2007;27:13938-48 pubmed..treatment or by blocking of ephrin A ligands with EphA fusion proteins, or by genetic manipulation leading to ephrin A2/A5 mutant mice, the spinal cord neurites loose their preference for the membranes of corresponding axial ..
- Shaut C, Saneyoshi C, Morgan E, Knosp W, Sexton D, Stadler H. HOXA13 directly regulates EphA6 and EphA7 expression in the genital tubercle vascular endothelia. Dev Dyn. 2007;236:951-60 pubmed..Together these findings indicate that HOXA13 directly regulates EphA6 and EphA7 in the developing GT and identifies the GT vascular endothelia as a novel site for HOXA13-dependent expression of EphA6 and EphA7. ..
- Ting M, Wu N, Roybal P, Sun J, Liu L, Yen Y, et al. EphA4 as an effector of Twist1 in the guidance of osteogenic precursor cells during calvarial bone growth and in craniosynostosis. Development. 2009;136:855-64 pubmed publisher..the neural crest-mesoderm boundary within the coronal suture, as well as with a reduction in the expression of ephrin A2 (Efna2), ephrin A4 (Efna4) and EphA4 in the coronal suture...
- Park E, Kim Y, Noh H, Lee H, Yoo S, Park S. EphA/ephrin-A signaling is critically involved in region-specific apoptosis during early brain development. Cell Death Differ. 2013;20:169-80 pubmed publisher..Together, our results suggest that brain region-specific PCD may occur in a region where EphAs cluster with neighboring ephrin-As through cell-cell contact. ..