Gene Symbol: Plxna2
Description: plexin A2
Alias: 2810428A13Rik, AA589422, AW457381, OCT, PlexA2, Plxn2, mKIAA0463, plexin-A2, plex 2, plexin-2
Species: mouse
Products:     Plxna2

Top Publications

  1. Bouvrée K, Brunet I, del Toro R, Gordon E, Prahst C, Cristofaro B, et al. Semaphorin3A, Neuropilin-1, and PlexinA1 are required for lymphatic valve formation. Circ Res. 2012;111:437-45 pubmed publisher
    ..Our data demonstrate an essential direct function of Sema3A-Nrp1-PlexinA1 signaling in lymphatic valve formation. ..
  2. Renaud J, Kerjan G, Sumita I, Zagar Y, Georget V, Kim D, et al. Plexin-A2 and its ligand, Sema6A, control nucleus-centrosome coupling in migrating granule cells. Nat Neurosci. 2008;11:440-9 pubmed publisher
    ..In plexin-A2-deficient (Plxna2(-/-)) mice, which were generated by homologous recombination, many granule cells remained in the molecular layer, ..
  3. Cheng H, Bagri A, Yaron A, Stein E, Pleasure S, Tessier Lavigne M. Plexin-A3 mediates semaphorin signaling and regulates the development of hippocampal axonal projections. Neuron. 2001;32:249-63 pubmed
    ..Analysis of plexin-A3 knockout mice shows that plexin-A3 contributes to Sema3F and Sema3A signaling and that plexin-A3 regulates the development of hippocampal axonal projections in vivo. ..
  4. Kameyama T, Murakami Y, Suto F, Kawakami A, Takagi S, Hirata T, et al. Identification of plexin family molecules in mice. Biochem Biophys Res Commun. 1996;226:396-402 pubmed
    ..Thus, we named these two proteins mouse plexin 2 and mouse plexin 3. We obtained mouse plexin 3 cDNA clones in which a part of protein-coding region was deleted...
  5. Vincentz J, Barnes R, Rodgers R, Firulli B, Conway S, Firulli A. An absence of Twist1 results in aberrant cardiac neural crest morphogenesis. Dev Biol. 2008;320:131-9 pubmed publisher
    ..Within the Twist1(-/-) neural crest cell populations that do emigrate to the OFT, a Hand-expressing subpopulation displays defective maturation, tracking, and, presumably, cell-cell adhesion, further compromising cNCC morphogenesis. ..
  6. Tawarayama H, Yoshida Y, Suto F, Mitchell K, Fujisawa H. Roles of semaphorin-6B and plexin-A2 in lamina-restricted projection of hippocampal mossy fibers. J Neurosci. 2010;30:7049-60 pubmed publisher
    ..of neural repellent Semaphorin-6A (Sema6A), a class 6 transmembrane semaphorin, and its receptors, plexin-A2 (PlxnA2) and PlxnA4, in mossy fiber projection and have proposed that PlxnA4-expressing mossy fibers are principally ..
  7. Takahashi T, Fournier A, Nakamura F, Wang L, Murakami Y, Kalb R, et al. Plexin-neuropilin-1 complexes form functional semaphorin-3A receptors. Cell. 1999;99:59-69 pubmed
    ..Sema3A treatment leads to the redistribution of growth cone NP-1 and plexin into clusters. Thus, physiologic Sema3A receptors consist of NP-1/plexin complexes. ..
  8. Murakami Y, Suto F, Shimizu M, Shinoda T, Kameyama T, Fujisawa H. Differential expression of plexin-A subfamily members in the mouse nervous system. Dev Dyn. 2001;220:246-58 pubmed
  9. Tamagnone L, Artigiani S, Chen H, He Z, Ming G, Song H, et al. Plexins are a large family of receptors for transmembrane, secreted, and GPI-anchored semaphorins in vertebrates. Cell. 1999;99:71-80 pubmed
    ..We conclude that plexins are receptors for multiple (and perhaps all) classes of semaphorins, either alone or in combination with neuropilins, and trigger a novel signal transduction pathway controlling cell repulsion. ..

More Information


  1. Brown C, Feiner L, Lu M, Li J, Ma X, Webber A, et al. PlexinA2 and semaphorin signaling during cardiac neural crest development. Development. 2001;128:3071-80 pubmed
    ..These data suggest a parallel between the function of semaphorin signaling in the central nervous system and in the patterning of cardiac neural crest in the periphery. ..
  2. Rohm B, Ottemeyer A, Lohrum M, Puschel A. Plexin/neuropilin complexes mediate repulsion by the axonal guidance signal semaphorin 3A. Mech Dev. 2000;93:95-104 pubmed
    ..These data suggest that functional semaphorin receptors contain plexins as signal-transducing and neuropilins as ligand-binding subunits. ..
  3. Suto F, Tsuboi M, Kamiya H, Mizuno H, Kiyama Y, Komai S, et al. Interactions between plexin-A2, plexin-A4, and semaphorin 6A control lamina-restricted projection of hippocampal mossy fibers. Neuron. 2007;53:535-47 pubmed
  4. Feiner L, Webber A, Brown C, Lu M, Jia L, Feinstein P, et al. Targeted disruption of semaphorin 3C leads to persistent truncus arteriosus and aortic arch interruption. Development. 2001;128:3061-70 pubmed
    ..Their entry is disrupted in semaphorin 3C mutant mice. These data suggest that semaphorin 3C promotes crest cell migration into the proximal cardiac outflow tract. ..
  5. Schwarz Q, Waimey K, Golding M, Takamatsu H, Kumanogoh A, Fujisawa H, et al. Plexin A3 and plexin A4 convey semaphorin signals during facial nerve development. Dev Biol. 2008;324:1-9 pubmed publisher
    ..Even though all four A-type plexins were expressed in embryonic motor neurons, PLXNA1 and PLXNA2 were not essential for facial nerve development...
  6. Toyofuku T, Yoshida J, Sugimoto T, Yamamoto M, Makino N, Takamatsu H, et al. Repulsive and attractive semaphorins cooperate to direct the navigation of cardiac neural crest cells. Dev Biol. 2008;321:251-62 pubmed publisher
    ..We therefore conclude that the coordination of repulsive cues provided by Sema6A/Sema6B through Plexin-A2 paired with the attractive cue by Sema3C through Plexin-D1 is required for the precise navigation of migrating cardiac NCCs. ..
  7. Jain R, Engleka K, Rentschler S, Manderfield L, Li L, Yuan L, et al. Cardiac neural crest orchestrates remodeling and functional maturation of mouse semilunar valves. J Clin Invest. 2011;121:422-30 pubmed publisher
    ..Hence, defects of cardiac neural crest can result in functionally abnormal semilunar valves and concomitant aortic arch artery abnormalities. ..
  8. High F, Zhang M, Proweller A, Tu L, Parmacek M, Pear W, et al. An essential role for Notch in neural crest during cardiovascular development and smooth muscle differentiation. J Clin Invest. 2007;117:353-63 pubmed
    ..These results provide a molecular and cellular framework for understanding the role of Notch signaling in the etiology of congenital heart disease. ..
  9. High F, Jain R, Stoller J, Antonucci N, Lu M, Loomes K, et al. Murine Jagged1/Notch signaling in the second heart field orchestrates Fgf8 expression and tissue-tissue interactions during outflow tract development. J Clin Invest. 2009;119:1986-96 pubmed publisher
  10. Janssen B, Robinson R, Pérez Brangulí F, Bell C, Mitchell K, Siebold C, et al. Structural basis of semaphorin-plexin signalling. Nature. 2010;467:1118-22 pubmed publisher
    ..regions of plexins B1 and A2 with semaphorin ectodomains (human PLXNB1(1-2)-SEMA4D(ecto) and murine PlxnA2(1-4)-Sema6A(ecto)), plus unliganded structures of PlxnA2(1-4) and Sema6A(ecto)...
  11. Rünker A, Little G, Suto F, Fujisawa H, Mitchell K. Semaphorin-6A controls guidance of corticospinal tract axons at multiple choice points. Neural Dev. 2008;3:34 pubmed publisher the guidance of CST axons, we have examined this tract in mutants of Semaphorin-6A (Sema6A), Plexin-A2 (PlxnA2) and Plexin-A4 (PlxnA4)...
  12. Mesbah K, Camus A, Babinet C, Barra J. Mutation in the Trapalpha/Ssr1 gene, encoding translocon-associated protein alpha, results in outflow tract morphogenetic defects. Mol Cell Biol. 2006;26:7760-71 pubmed
  13. Matsuoka R, Chivatakarn O, Badea T, SAMUELS I, Cahill H, Katayama K, et al. Class 5 transmembrane semaphorins control selective Mammalian retinal lamination and function. Neuron. 2011;71:460-73 pubmed publisher
    ..These findings define a set of ligands and receptors required for the establishment of inner retinal lamination and function. ..
  14. Nogi T, Yasui N, Mihara E, Matsunaga Y, Noda M, Yamashita N, et al. Structural basis for semaphorin signalling through the plexin receptor. Nature. 2010;467:1123-7 pubmed publisher
    ..Here we report the crystal structures of the semaphorin 6A (Sema6A) receptor-binding fragment and the plexin A2 (PlxnA2) ligand-binding fragment in both their pre-signalling (that is, before binding) and signalling (after ..
  15. Jiang Q, Arnold S, Heanue T, Kilambi K, Doan B, Kapoor A, et al. Functional loss of semaphorin 3C and/or semaphorin 3D and their epistatic interaction with ret are critical to Hirschsprung disease liability. Am J Hum Genet. 2015;96:581-96 pubmed publisher
    ..Thus, semaphorin 3C/3D signaling is an evolutionarily conserved regulator of ENS development whose dys-regulation is a cause of enteric aganglionosis. ..
  16. Chandler R, Magnuson T. The SWI/SNF BAF-A complex is essential for neural crest development. Dev Biol. 2016;411:15-24 pubmed publisher
  17. Matsuoka R, Jiang Z, SAMUELS I, Nguyen Ba Charvet K, Sun L, Peachey N, et al. Guidance-cue control of horizontal cell morphology, lamination, and synapse formation in the mammalian outer retina. J Neurosci. 2012;32:6859-68 pubmed publisher
    ..These findings define molecular components required for outer retina lamination and ribbon synapse formation. ..
  18. Todorovic V, Frendewey D, Gutstein D, Chen Y, Freyer L, Finnegan E, et al. Long form of latent TGF-beta binding protein 1 (Ltbp1L) is essential for cardiac outflow tract septation and remodeling. Development. 2007;134:3723-32 pubmed
    ..This phenotype reveals a crucial role for Ltbp1L and matrix as extracellular regulators of Tgf-beta activity in heart organogenesis. ..
  19. Oh J, Kim H, Kim W, Lee Z, Ryoo H, Hwang S, et al. PlexinA2 mediates osteoblast differentiation via regulation of Runx2. J Bone Miner Res. 2012;27:552-62 pubmed publisher
    ..In a microarray analysis with mouse preosteoblast cells, we found that PlexinA2 (PlxnA2), a molecule previously known to mediate axon guidance in neural development, was upregulated by the osteogenic ..
  20. Guo C, Sun Y, Zhou B, Adam R, Li X, Pu W, et al. A Tbx1-Six1/Eya1-Fgf8 genetic pathway controls mammalian cardiovascular and craniofacial morphogenesis. J Clin Invest. 2011;121:1585-95 pubmed publisher
    ..Together, these findings reveal a Tbx1-Six1/Eya1-Fgf8 genetic pathway that is crucial for mammalian cardiocraniofacial morphogenesis and provide insights into the pathogenesis of human del22q11 syndromes. ..
  21. Manthey A, Lachke S, FitzGerald P, Mason R, Scheiblin D, McDonald J, et al. Loss of Sip1 leads to migration defects and retention of ectodermal markers during lens development. Mech Dev. 2014;131:86-110 pubmed publisher
  22. Kerkela R, Kockeritz L, MacAulay K, Zhou J, Doble B, Beahm C, et al. Deletion of GSK-3beta in mice leads to hypertrophic cardiomyopathy secondary to cardiomyoblast hyperproliferation. J Clin Invest. 2008;118:3609-18 pubmed publisher
    ..Although controversy over the teratogenic effects of lithium remains, our studies suggest that caution should be exercised in the use of newer, more potent drugs targeting GSK-3 in women of childbearing age. ..
  23. Renaud J, Chédotal A. Time-lapse analysis of tangential migration in Sema6A and PlexinA2 knockouts. Mol Cell Neurosci. 2014;63:49-59 pubmed publisher
    ..This study reveals that defects of tangential migration can be detected in bipolar granule cells before the initiation of radial migration. Our results also directly confirm that the absence of Sema6A does not perturb radial migration. ..
  24. Escalante A, Murillo B, Morenilla Palao C, Klar A, Herrera E. Zic2-dependent axon midline avoidance controls the formation of major ipsilateral tracts in the CNS. Neuron. 2013;80:1392-406 pubmed publisher
    ..Together with previous reports, our data reveal a critical role for Zic2 as a determinant of axon midline avoidance in the CNS across species and pathways. ..
  25. Hamblet N, Lijam N, Ruiz Lozano P, Wang J, Yang Y, Luo Z, et al. Dishevelled 2 is essential for cardiac outflow tract development, somite segmentation and neural tube closure. Development. 2002;129:5827-38 pubmed
    ..Expression of Pitx2 and plexin A2 was attenuated in Dvl2 null mutants, suggesting a defect in cardiac neural crest development during outflow ..
  26. Lin L, Cui L, Zhou W, Dufort D, Zhang X, Cai C, et al. Beta-catenin directly regulates Islet1 expression in cardiovascular progenitors and is required for multiple aspects of cardiogenesis. Proc Natl Acad Sci U S A. 2007;104:9313-8 pubmed
    ..Our findings demonstrate that beta-catenin signaling regulates proliferation and survival of cardiac progenitors. ..
  27. Kuroiwa A, Suto F, Fujisawa H, Matsuda Y. Chromosome assignment of four plexin A genes (Plxna1, Plxna2, Plxna3, Plxna4) in mouse, rat, Syrian hamster and Chinese hamster. Cytogenet Cell Genet. 2001;92:127-9 pubmed
    We determined chromosome locations of four plexin A subfamily genes, Plxna1, Plxna2, Plxna3 and Plxna4, in four rodent species, mouse, rat, Syrian hamster and Chinese hamster, by fluorescence in situ hybridization...
  28. Li W, Xiong Y, Shang C, Twu K, Hang C, Yang J, et al. Brg1 governs distinct pathways to direct multiple aspects of mammalian neural crest cell development. Proc Natl Acad Sci U S A. 2013;110:1738-43 pubmed publisher
    ..Our findings reveal an important role for Brg1 and its downstream pathways in the survival, differentiation, and migration of the multipotent NCCs critical for mammalian cardiovascular development. ..
  29. Lin L, Bu L, Cai C, Zhang X, Evans S. Isl1 is upstream of sonic hedgehog in a pathway required for cardiac morphogenesis. Dev Biol. 2006;295:756-63 pubmed
    ..We find that expression of npn2 is downregulated in isl1-cre;smo mutants, suggesting an isl1/Shh/npn pathway required to affect morphogenesis at the anterior pole of the heart. ..
  30. Klisch T, Xi Y, Flora A, Wang L, Li W, Zoghbi H. In vivo Atoh1 targetome reveals how a proneural transcription factor regulates cerebellar development. Proc Natl Acad Sci U S A. 2011;108:3288-93 pubmed publisher
    ..This study expands current thinking about the transcriptional activities driving neuronal differentiation and provides a framework for further neurodevelopmental studies. ..
  31. Plein A, Calmont A, Fantin A, Denti L, Anderson N, Scambler P, et al. Neural crest-derived SEMA3C activates endothelial NRP1 for cardiac outflow tract septation. J Clin Invest. 2015;125:2661-76 pubmed publisher
    ..These findings elucidate a mechanism by which NCCs cooperate with endothelial cells in the developing OFT to enable the postnatal separation of the pulmonary and systemic circulation. ..
  32. Bisson J, Mills B, Paul Helt J, Zwaka T, Cohen E. Wnt5a and Wnt11 inhibit the canonical Wnt pathway and promote cardiac progenitor development via the Caspase-dependent degradation of AKT. Dev Biol. 2015;398:80-96 pubmed publisher
    ..Moreover, Akt inhibition restored SHF gene expression in Casp3 mutant ES cells. Taken together, these findings suggest that Wnt5a/Wnt11 inhibit β-catenin to promote SHF development through Caspase-dependent Akt degradation. ..
  33. Uchida Y, James J, Suto F, Mukouyama Y. Class 3 semaphorins negatively regulate dermal lymphatic network formation. Biol Open. 2015;4:1194-205 pubmed publisher
    ..The reciprocal phenotype in lymphatic branching between Sema3f;Sema3g double mutants and Nrp2 mutants suggest a complex NRP2 function that regulates LEC behavior both positively and negatively, through a binding with VEGFC or SEMA3s. ..
  34. Nakamura F, Ugajin K, Yamashita N, Okada T, Uchida Y, Taniguchi M, et al. Increased proximal bifurcation of CA1 pyramidal apical dendrites in sema3A mutant mice. J Comp Neurol. 2009;516:360-75 pubmed publisher
    ..Thus, Sema3A may facilitate the initial growth of CA1 apical dendrites via the activation of p35/Cdk5, which may in turn signal hippocampal development. ..
  35. Perälä N, Immonen T, Sariola H. The expression of plexins during mouse embryogenesis. Gene Expr Patterns. 2005;5:355-62 pubmed
    ..In the testis, Plxna1, Plxnb1 and Plxnc1 are expressed in the developing sex chords. This study shows that during development, plexins are expressed in specific and distinct patterns also in non-neuronal tissues. ..
  36. Lin C, Lin C, Chen C, Chen R, Zhou B, Chang C. The secondary heart field is a new site of calcineurin/Nfatc1 signaling for semilunar valve development. J Mol Cell Cardiol. 2012;52:1096-102 pubmed publisher
  37. Schleiffarth J, Person A, Martinsen B, Sukovich D, Neumann A, Baker C, et al. Wnt5a is required for cardiac outflow tract septation in mice. Pediatr Res. 2007;61:386-91 pubmed
  38. Matsuoka R, Nguyen Ba Charvet K, Parray A, Badea T, Chedotal A, Kolodkin A. Transmembrane semaphorin signalling controls laminar stratification in the mammalian retina. Nature. 2011;470:259-63 pubmed publisher
    ..Therefore, neuronal targeting to subdivisions of the IPL in the mammalian retina is directed by repulsive transmembrane guidance cues present on neuronal processes. ..
  39. Mesbah K, Harrelson Z, Théveniau Ruissy M, Papaioannou V, Kelly R. Tbx3 is required for outflow tract development. Circ Res. 2008;103:743-50 pubmed publisher
  40. Shimizu M, Murakami Y, Suto F, Fujisawa H. Determination of cell adhesion sites of neuropilin-1. J Cell Biol. 2000;148:1283-93 pubmed
    ..In addition, we demonstrated that the cell adhesion ligands for neuropilin-1 were proteins and distributed in embryonic mesenchymal cells but distinct from the class 3 semaphorins, VEGF, or plexins. ..
  41. Lepore J, Mericko P, Cheng L, Lu M, Morrisey E, Parmacek M. GATA-6 regulates semaphorin 3C and is required in cardiac neural crest for cardiovascular morphogenesis. J Clin Invest. 2006;116:929-39 pubmed
    ..These findings provide new insights into the conserved functions of the GATA-4, -5, and -6 subfamily members and identify GATA-6 and GATA-6-regulated genes as candidates involved in the pathogenesis of congenital heart disease. ..
  42. Kaartinen V, Dudas M, Nagy A, Sridurongrit S, Lu M, Epstein J. Cardiac outflow tract defects in mice lacking ALK2 in neural crest cells. Development. 2004;131:3481-90 pubmed
    ..Thus, the type I BMP receptor ALK2 plays an essential cell-autonomous role in the development of the cardiac outflow tract and aortic arch derivatives. ..
  43. Li J, Zhu X, Chen M, Cheng L, Zhou D, Lu M, et al. Myocardin-related transcription factor B is required in cardiac neural crest for smooth muscle differentiation and cardiovascular development. Proc Natl Acad Sci U S A. 2005;102:8916-21 pubmed
  44. Kong Y, Janssen B, Malinauskas T, Vangoor V, Coles C, Kaufmann R, et al. Structural Basis for Plexin Activation and Regulation. Neuron. 2016;91:548-60 pubmed publisher
    ..Here we present crystal structures of PlxnA (PlxnA1, PlxnA2, and PlxnA4) full ectodomains...
  45. Mitsogiannis M, Little G, Mitchell K. Semaphorin-Plexin signaling influences early ventral telencephalic development and thalamocortical axon guidance. Neural Dev. 2017;12:6 pubmed publisher
    ..and neuroanatomical analyses of thalamocortical wiring and subpallial development in Sema6a and Plxna2; Plxna4 null mutant mice and analyzed the expression of these genes in relevant structures...
  46. Marguerie A, Bajolle F, Zaffran S, Brown N, Dickson C, Buckingham M, et al. Congenital heart defects in Fgfr2-IIIb and Fgf10 mutant mice. Cardiovasc Res. 2006;71:50-60 pubmed
    ..Fgfr2-IIIb and Fgf10 mutant mice provide new models for common components of congenital heart disease. ..
  47. Bernard F, Moreau Fauvarque C, Heitz Marchaland C, Zagar Y, Dumas L, Fouquet S, et al. Role of transmembrane semaphorin Sema6A in oligodendrocyte differentiation and myelination. Glia. 2012;60:1590-604 pubmed publisher
    ..These results suggest that Sema6A might have a role in myelination by controlling oligodendrocyte differentiation. ..
  48. Liu S, Liu F, Schneider A, St Amand T, Epstein J, Gutstein D. Distinct cardiac malformations caused by absence of connexin 43 in the neural crest and in the non-crest neural tube. Development. 2006;133:2063-73 pubmed
    ..Rather, this study suggests a novel function for Cx43 in which Cx43 acts through non-crest neuroepithelial cells to suppress cellular delamination from the neural tube and thereby preserve normal OFT development. ..
  49. Nogi T, Mihara E, Yasui N, Takagi J. Immunoaffinity Purification of the Glycosylated Extracellular Fragment of Mouse Plexin A2 Produced in a Mammalian Expression System. Methods Mol Biol. 2017;1493:57-72 pubmed
    ..procedures for protein production and purification that we utilized in the crystallographic study of the mouse Plexin A2 (mPlxnA2) extracellular fragment, including the sema domain...
  50. Kodo K, Nishizawa T, Furutani M, Arai S, Yamamura E, Joo K, et al. GATA6 mutations cause human cardiac outflow tract defects by disrupting semaphorin-plexin signaling. Proc Natl Acad Sci U S A. 2009;106:13933-8 pubmed publisher
    ..Genes encoding the neurovascular guiding molecule semaphorin 3C (SEMA3C) and its receptor plexin A2 (PLXNA2) appear to be regulated directly by GATA6, and both GATA6 mutant proteins failed to transactivate these ..
  51. Takahashi K, Ishida M, Hirokawa K, Takahashi H. Expression of the semaphorins Sema 3D and Sema 3F in the developing parathyroid and thymus. Dev Dyn. 2008;237:1699-708 pubmed publisher
  52. Sun L, Brady C, Cahill H, Al Khindi T, Sakuta H, Dhande O, et al. Functional assembly of accessory optic system circuitry critical for compensatory eye movements. Neuron. 2015;86:971-984 pubmed publisher
    ..b>Plexin A2 and A4, two Sema6A binding partners, are expressed in MTN cells, attract Sema6A(+) On DSGC axons, and mediate ..
  53. Aghajanian H, Cho Y, Rizer N, Wang Q, Li L, Degenhardt K, et al. Pdgfr? functions in endothelial-derived cells to regulate neural crest cells and the development of the great arteries. Dis Model Mech. 2017;10:1101-1108 pubmed publisher
    ..Our data suggest that loss of Pdgfra in endothelial-derived mesenchyme in the outflow tract endocardial cushions leads to a secondary defect in neural crest migration during development. ..