Gene Symbol: Plxnd1
Description: plexin D1
Alias: 6230425C21Rik, b2b1863Clo, b2b553Clo, plexin-D1
Species: mouse
Products:     Plxnd1

Top Publications

  1. Holl E, O Connor B, Holl T, Roney K, Zimmermann A, JHA S, et al. Plexin-D1 is a novel regulator of germinal centers and humoral immune responses. J Immunol. 2011;186:5603-11 pubmed publisher
    ..Plexin-D1 expression was increased following B cell activation, and PlxnD1(-/-) mice exhibited defective GC reactions during T-dependent immune activation...
  2. Gu C, Yoshida Y, Livet J, Reimert D, Mann F, Merte J, et al. Semaphorin 3E and plexin-D1 control vascular pattern independently of neuropilins. Science. 2005;307:265-8 pubmed
    ..These findings reveal an unexpected semaphorin signaling pathway and define a mechanism for controlling vascular patterning. ..
  3. Toyofuku T, Yabuki M, Kamei J, Kamei M, Makino N, Kumanogoh A, et al. Semaphorin-4A, an activator for T-cell-mediated immunity, suppresses angiogenesis via Plexin-D1. EMBO J. 2007;26:1373-84 pubmed
    ..The effects of Sema4A on endothelial cells are dependent on its ability to suppress VEGF-mediated Rac activation and integrin-dependent cell adhesion. It thus appears that Sema4A-Plexin-D1 signaling negatively regulates angiogenesis. ..
  4. van der Zwaag B, Hellemons A, Leenders W, Burbach J, Brunner H, Padberg G, et al. PLEXIN-D1, a novel plexin family member, is expressed in vascular endothelium and the central nervous system during mouse embryogenesis. Dev Dyn. 2002;225:336-43 pubmed
    ..protein, and examined the expression pattern during mouse embryogenesis of a positional candidate gene, PLEXIN-D1 (PLXND1). The cDNA for PLXND1 is 7095 base pairs in length, coding for a predicted protein of 1925 amino acids...
  5. 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. ..
  6. Zhang Y, Singh M, Degenhardt K, Lu M, Bennett J, Yoshida Y, et al. Tie2Cre-mediated inactivation of plexinD1 results in congenital heart, vascular and skeletal defects. Dev Biol. 2009;325:82-93 pubmed publisher
    ..These results demonstrate an important role for PlexinD1 in embryonic and adult vasculature. ..
  7. Chauvet S, Cohen S, Yoshida Y, Fekrane L, Livet J, Gayet O, et al. Gating of Sema3E/PlexinD1 signaling by neuropilin-1 switches axonal repulsion to attraction during brain development. Neuron. 2007;56:807-22 pubmed
    ..Our data therefore reveal a "gating" function of neuropilins in semaphorin-plexin signaling during the assembly of forebrain neuronal circuits. ..
  8. Molyneaux B, Arlotta P, Hirata T, Hibi M, Macklis J. Fezl is required for the birth and specification of corticospinal motor neurons. Neuron. 2005;47:817-31 pubmed
  9. Watakabe A, Ohsawa S, Hashikawa T, Yamamori T. Binding and complementary expression patterns of semaphorin 3E and plexin D1 in the mature neocortices of mice and monkeys. J Comp Neurol. 2006;499:258-73 pubmed
    ..By an in vitro binding experiment, we provide evidence that Plexin D1 is the specific receptor for Sema3E...

More Information


  1. Pecho Vrieseling E, Sigrist M, Yoshida Y, Jessell T, Arber S. Specificity of sensory-motor connections encoded by Sema3e-Plxnd1 recognition. Nature. 2009;459:842-6 pubmed publisher
    ..expression of the class 3 semaphorin Sema3e by selected motor neuron pools, and its high-affinity receptor plexin D1 (Plxnd1) by proprioceptive sensory neurons, is a critical determinant of synaptic specificity in sensory-motor ..
  2. 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. ..
  3. Choi Y, Duke Cohan J, Chen W, Liu B, Rossy J, Tabarin T, et al. Dynamic control of ?1 integrin adhesion by the plexinD1-sema3E axis. Proc Natl Acad Sci U S A. 2014;111:379-84 pubmed publisher
    ..Our results demonstrate plexin-tunable molecular features of integrin adhesion with broad implications for many cellular processes. ..
  4. 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
  5. van Battum E, Gunput R, Lemstra S, Groen E, Yu K, Adolfs Y, et al. The intracellular redox protein MICAL-1 regulates the development of hippocampal mossy fibre connections. Nat Commun. 2014;5:4317 pubmed publisher
  6. Fame R, Dehay C, Kennedy H, Macklis J. Subtype-Specific Genes that Characterize Subpopulations of Callosal Projection Neurons in Mouse Identify Molecularly Homologous Populations in Macaque Cortex. Cereb Cortex. 2017;27:1817-1830 pubmed publisher
    ..Together, these data inform future studies regarding CPN subpopulations that are unique to primates and rodents, and indicate putative evolutionary relationships. ..
  7. Moriya J, Minamino T, Tateno K, Okada S, Uemura A, Shimizu I, et al. Inhibition of semaphorin as a novel strategy for therapeutic angiogenesis. Circ Res. 2010;106:391-8 pubmed publisher
    ..These results indicate that inhibition of Sema3E may be a novel strategy for therapeutic angiogenesis, especially when VEGF is ineffective. ..
  8. Gay C, Zygmunt T, Torres Vazquez J. Diverse functions for the semaphorin receptor PlexinD1 in development and disease. Dev Biol. 2011;349:1-19 pubmed publisher
    ..recently, little was known about the function of PlexinD1, the sole member of the vertebrate-specific PlexinD (PlxnD1) subfamily...
  9. Ueda Y, Kondo N, Ozawa M, Yasuda K, Tomiyama T, Kinashi T. Sema3e/Plexin D1 Modulates Immunological Synapse and Migration of Thymocytes by Rap1 Inhibition. J Immunol. 2016;196:3019-31 pubmed publisher
    ..inhibited Rap1 activation and LFA-1-dependent adhesion through the GTPase-activating protein activity of plexin D1. Sema3e inhibited Rap1 activation of thymocytes in response to chemokines and TCR stimulation, LFA-mediated ..
  10. Choi Y, Duke Cohan J, Tan J, Gui J, Singh M, Epstein J, et al. Plxnd1 expression in thymocytes regulates their intrathymic migration while that in thymic endothelium impacts medullary topology. Front Immunol. 2013;4:392 pubmed publisher
    An important role for plexinD1 in thymic development is inferred from studies of germline Plxnd1 knockout (KO) mice where mislocalized CD69(+) thymocytes as well as ectopic thymic subcapsular medullary structures were observed...
  11. 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. ..
  12. Burk K, Mire E, Bellon A, Hocine M, Guillot J, Moraes F, et al. Post-endocytic sorting of Plexin-D1 controls signal transduction and development of axonal and vascular circuits. Nat Commun. 2017;8:14508 pubmed publisher
    ..Thus, intracellular sorting steps that occur after receptor internalization by endocytosis provide a critical level of control of cellular responses to guidance signals. ..
  13. Sakurai A, Gavard J, Annas Linhares Y, Basile J, Amornphimoltham P, Palmby T, et al. Semaphorin 3E initiates antiangiogenic signaling through plexin D1 by regulating Arf6 and R-Ras. Mol Cell Biol. 2010;30:3086-98 pubmed publisher
    ..revealed that a class III semaphorin, semaphorin 3E (Sema3E), acts through a single-pass transmembrane receptor, plexin D1, to provide a repulsive cue for plexin D1-expressing endothelial cells, thus providing a highly conserved and ..
  14. Bribian A, Nocentini S, Llorens F, Gil V, Mire E, Reginensi D, et al. Sema3E/PlexinD1 regulates the migration of hem-derived Cajal-Retzius cells in developing cerebral cortex. Nat Commun. 2014;5:4265 pubmed publisher
    ..Indeed, absence of Sema3E/PlexinD1 signalling increased the migratory properties of CR cells. This modulation implies negative effects on CXCL12/CXCR4 signalling and increased ADF/Cofilin activity. ..
  15. Worzfeld T, Swiercz J, Sentürk A, Genz B, Korostylev A, Deng S, et al. Genetic dissection of plexin signaling in vivo. Proc Natl Acad Sci U S A. 2014;111:2194-9 pubmed publisher
    ..Our genetic analyses uncover the in vivo context-dependence and functional specificity of individual plexin-mediated signaling pathways during development. ..
  16. Azim E, Jabaudon D, Fame R, Macklis J. SOX6 controls dorsal progenitor identity and interneuron diversity during neocortical development. Nat Neurosci. 2009;12:1238-47 pubmed publisher
    ..These data indicate that SOX6 is a central regulator of both progenitor and cortical interneuron diversity during neocortical development. ..
  17. Lu K, Evans S, Hirano S, Liu F. Dual role for Islet-1 in promoting striatonigral and repressing striatopallidal genetic programs to specify striatonigral cell identity. Proc Natl Acad Sci U S A. 2014;111:E168-77 pubmed publisher
    ..The dual action of developmental control by Isl1 in promoting appropriate striatonigral but repressing inappropriate striatopallidal genetic profiles may ensure sharpening of the striatonigral identity during development. ..
  18. Vilz T, Moepps B, Engele J, Molly S, Littman D, Schilling K. The SDF-1/CXCR4 pathway and the development of the cerebellar system. Eur J Neurosci. 2005;22:1831-9 pubmed
    ..Consequently, nascent pontine nuclei in CXCR4-deficient animals are hypoplastic. Moreover, they fail to express plexin D1, suggesting that SDF-1/CXCR4 signalling may also impinge on axon guidance critical to the orderly formation of ..
  19. Wang F, Eagleson K, Levitt P. Positive regulation of neocortical synapse formation by the Plexin-D1 receptor. Brain Res. 2015;1616:157-165 pubmed publisher
    ..The data indicate that Plexin-D1 operates in a cell context-specific fashion, mediating different synaptogenic outcomes depending upon neuron type. ..
  20. Oh W, Gu C. Establishment of neurovascular congruency in the mouse whisker system by an independent patterning mechanism. Neuron. 2013;80:458-69 pubmed publisher
  21. Liu X, Uemura A, Fukushima Y, Yoshida Y, Hirashima M. Semaphorin 3G Provides a Repulsive Guidance Cue to Lymphatic Endothelial Cells via Neuropilin-2/PlexinD1. Cell Rep. 2016;17:2299-2311 pubmed publisher
    ..Sema3G induces cell collapse in an Nrp2/PlexinD1-dependent manner. Our findings shed light on a molecular mechanism by which LECs are distributed away from arteries and form a branching network during lymphatic vascular development. ..
  22. Wanschel A, Seibert T, Hewing B, Ramkhelawon B, Ray T, van Gils J, et al. Neuroimmune guidance cue Semaphorin 3E is expressed in atherosclerotic plaques and regulates macrophage retention. Arterioscler Thromb Vasc Biol. 2013;33:886-93 pubmed publisher
  23. Meadows S, Ratliff L, Singh M, Epstein J, Cleaver O. Resolution of defective dorsal aortae patterning in Sema3E-deficient mice occurs via angiogenic remodeling. Dev Dyn. 2013;242:580-90 pubmed publisher
    ..Our observations explain how Sema3E(-) (/) (-) mice survive throughout development and into adulthood, despite severe initial vascular defects. ..
  24. Shang G, Brautigam C, Chen R, Lu D, Torres Vázquez J, Zhang X. Structure analyses reveal a regulated oligomerization mechanism of the PlexinD1/GIPC/myosin VI complex. elife. 2017;6: pubmed publisher
    ..GIPCs and myosin VI interact through two distinct interfaces and form an open-ended alternating array. Our data support that this alternating array underlies the oligomerization of the GIPC/Myosin VI complexes in solution and cells. ..
  25. 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. ..
  26. Gitler A, Lu M, Epstein J. PlexinD1 and semaphorin signaling are required in endothelial cells for cardiovascular development. Dev Cell. 2004;7:107-16 pubmed
    ..Thus, molecular programs that mediate axon guidance in the central nervous system also function in endothelial cells to orchestrate critical aspects of cardiac morphogenesis. ..
  27. Ding J, Oh W, Sabatini B, Gu C. Semaphorin 3E-Plexin-D1 signaling controls pathway-specific synapse formation in the striatum. Nat Neurosci. 2011;15:215-23 pubmed publisher
    ..that Sema3e (encoding Sema3E) is highly expressed in thalamostriatal projection neurons, whereas in the striatum Plxnd1 (encoding Plexin-D1) is selectively expressed in direct-pathway medium spiny neurons (MSNs)...
  28. Rademacher S, Verheijen B, Hensel N, Peters M, Bora G, Brandes G, et al. Metalloprotease-mediated cleavage of PlexinD1 and its sequestration to actin rods in the motoneuron disease spinal muscular atrophy (SMA). Hum Mol Genet. 2017;26:3946-3959 pubmed publisher
    ..Our data suggest a novel disease mechanism for SMA involving formation of actin rods as a molecular sink for a cleaved PlexinD1 fragment leading to dysregulation of receptor signaling. ..
  29. Bellon A, Luchino J, Haigh K, Rougon G, Haigh J, Chauvet S, et al. VEGFR2 (KDR/Flk1) signaling mediates axon growth in response to semaphorin 3E in the developing brain. Neuron. 2010;66:205-19 pubmed publisher
    ..This mechanism provides an explanation as to how a semaphorin can activate an axon growth promoting response in developing neurons. ..
  30. Deloulme J, Gory Fauré S, Mauconduit F, Chauvet S, Jonckheere J, Boulan B, et al. Microtubule-associated protein 6 mediates neuronal connectivity through Semaphorin 3E-dependent signalling for axonal growth. Nat Commun. 2015;6:7246 pubmed publisher
    ..We conclude that MAP6 is critical to interface guidance molecules with intracellular signalling effectors during the development of cerebral axon tracts. ..
  31. Uesugi K, Oinuma I, Katoh H, Negishi M. Different requirement for Rnd GTPases of R-Ras GAP activity of Plexin-C1 and Plexin-D1. J Biol Chem. 2009;284:6743-51 pubmed publisher
    ..Therefore, R-Ras GAP activity is a common function of plexin subfamilies but the regulation of R-Ras GAP activity of plexins by Rnd proteins is different among plexin subfamilies. ..
  32. Li S, Zhou D, Lu M, Morrisey E. Advanced cardiac morphogenesis does not require heart tube fusion. Science. 2004;305:1619-22 pubmed
  33. Chung L, Yang T, Huang H, Hsu S, Cheng H, Huang P. Semaphorin signaling facilitates cleft formation in the developing salivary gland. Development. 2007;134:2935-45 pubmed Sema3A and Sema3C in an additive manner, and can be abolished by decreasing the expression of plexin A2 or plexin D1. VEGF, another known Npn1 ligand, has no apparent effects on SMG development...
  34. Minchin J, Dahlman I, Harvey C, Mejhert N, Singh M, Epstein J, et al. Plexin D1 determines body fat distribution by regulating the type V collagen microenvironment in visceral adipose tissue. Proc Natl Acad Sci U S A. 2015;112:4363-8 pubmed publisher
    Genome-wide association studies have implicated PLEXIN D1 (PLXND1) in body fat distribution and type 2 diabetes. However, a role for PLXND1 in regional adiposity and insulin resistance is unknown...
  35. Kanda T, Yoshida Y, Izu Y, Nifuji A, Ezura Y, Nakashima K, et al. PlexinD1 deficiency induces defects in axial skeletal morphogenesis. J Cell Biochem. 2007;101:1329-37 pubmed
    ..However, PlexinD1 heterozygous knockout did not reveal defects in new bone formation. In conclusion, PlexinD1 is involved in the patterning of axial skeletogenesis. ..
  36. Meadows S, Cleaver O. Annexin A3 Regulates Early Blood Vessel Formation. PLoS ONE. 2015;10:e0132580 pubmed publisher
    ..Our results are the first to reveal an in vivo function for Anxa3 during vascular development and represent a previously unexplored aspect of annexin biology. ..
  37. Cariboni A, André V, Chauvet S, Cassatella D, Davidson K, Caramello A, et al. Dysfunctional SEMA3E signaling underlies gonadotropin-releasing hormone neuron deficiency in Kallmann syndrome. J Clin Invest. 2015;125:2413-28 pubmed publisher
    ..Recombinant wild-type SEMA3E protected maturing GnRH neurons from cell death by triggering a plexin D1-dependent (PLXND1-dependent) activation of PI3K-mediated survival signaling...
  38. Heisig J, Weber D, Englberger E, Winkler A, Kneitz S, Sung W, et al. Target gene analysis by microarrays and chromatin immunoprecipitation identifies HEY proteins as highly redundant bHLH repressors. PLoS Genet. 2012;8:e1002728 pubmed publisher
    ..These data clearly establish the three HEY bHLH factors as highly redundant transcriptional repressors in vitro and in vivo, which explains the combinatorial action observed in different tissues with overlapping expression. ..
  39. Fukuhara K, Imai F, Ladle D, Katayama K, Leslie J, Arber S, et al. Specificity of monosynaptic sensory-motor connections imposed by repellent Sema3E-PlexinD1 signaling. Cell Rep. 2013;5:748-58 pubmed publisher
    ..A semaphorin-based system of motor neuron recognition and repulsion therefore contributes to the formation of specific sensory-motor connections in mammalian spinal cord. ..
  40. Mata A, Gil V, Pérez Clausell J, Dasilva M, González Calixto M, Soriano E, et al. New functions of Semaphorin 3E and its receptor PlexinD1 during developing and adult hippocampal formation. Sci Rep. 2018;8:1381 pubmed publisher
    ..Lastly, Sema3E mutant mice displayed increased network excitability both in the dentate gyrus and the hippocampus proper. ..
  41. Darwich R, Li W, Yamak A, Komati H, Andelfinger G, Sun K, et al. KLF13 is a genetic modifier of the Holt-Oram syndrome gene TBX5. Hum Mol Genet. 2017;26:942-954 pubmed publisher
    ..The data also suggest that, in human, KLF13 may be a genetic modifier of the Holt-Oram Syndrome gene TBX5. ..
  42. Lizen B, Hutlet B, Bissen D, Sauvegarde D, Hermant M, Ahn M, et al. HOXA5 localization in postnatal and adult mouse brain is suggestive of regulatory roles in postmitotic neurons. J Comp Neurol. 2017;525:1155-1175 pubmed publisher
    ..J. Comp. Neurol. 525:1155-1175, 2017. © 2016 Wiley Periodicals, Inc. ..
  43. Tomas Roca L, Tsaalbi Shtylik A, Jansen J, Singh M, Epstein J, Altunoglu U, et al. De novo mutations in PLXND1 and REV3L cause Möbius syndrome. Nat Commun. 2015;6:7199 pubmed publisher
    ..Here, we report de novo mutations affecting two genes, PLXND1 and REV3L in MBS patients...
  44. Holl E, Roney K, Allen I, Steinbach E, Arthur J, Buntzman A, et al. Plexin-B2 and Plexin-D1 in dendritic cells: expression and IL-12/IL-23p40 production. PLoS ONE. 2012;7:e43333 pubmed publisher
    ..To explore this, we utilized chimeric mice lacking Plxnb2 or Plxnd1. Absence of Plexin-B2 and Plexin-D1 on DCs did not affect the ability of these cells to upregulate costimulatory ..
  45. Yang Y, Garcia Verdugo J, Soriano Navarro M, Srinivasan R, Scallan J, Singh M, et al. Lymphatic endothelial progenitors bud from the cardinal vein and intersomitic vessels in mammalian embryos. Blood. 2012;120:2340-8 pubmed publisher
    ..Analyzing this process in Prox1-null embryos revealed that Prox1 activity is necessary for LEC progenitors to exit the CV. ..
  46. Suda K, Guo C, Oishi A, Ikeda S, Uemura A, Yoshimura N. Therapeutic potential of semaphorin 3E for the treatment of choroidal neovascularization. Invest Ophthalmol Vis Sci. 2014;55:4700-6 pubmed publisher
    ..These results indicate that Sema3E-PlexinD1 signaling is involved in the development of CNV. Stimulation of the pathway has therapeutic potential for CNV. Further studies are needed to evaluate the effects for clinical applications. ..
  47. Rattner A, Yu H, Williams J, Smallwood P, Nathans J. Endothelin-2 signaling in the neural retina promotes the endothelial tip cell state and inhibits angiogenesis. Proc Natl Acad Sci U S A. 2013;110:E3830-9 pubmed publisher
    ..The response to Edn2 is sufficiently potent that it overrides the activities of other homeostatic regulators of angiogenesis, such as Vegf. ..
  48. Kim J, Oh W, Gaiano N, Yoshida Y, Gu C. Semaphorin 3E-Plexin-D1 signaling regulates VEGF function in developmental angiogenesis via a feedback mechanism. Genes Dev. 2011;25:1399-411 pubmed publisher
    ..Together, these data reveal a novel role of Sema3E-Plexin-D1 function in modulating angiogenesis via a VEGF-induced feedback mechanism. ..
  49. Choi Y, Duke Cohan J, Ahmed W, Handley M, Mann F, Epstein J, et al. PlexinD1 glycoprotein controls migration of positively selected thymocytes into the medulla. Immunity. 2008;29:888-98 pubmed publisher
    ..CD69+ thymocytes remained in the cortex, maturing to form ectopic single positive (SP) thymocyte clusters in Plxnd1-deficient fetal liver cell-transplanted mice...
  50. Deck M, Lokmane L, Chauvet S, Mailhes C, Keita M, Niquille M, et al. Pathfinding of corticothalamic axons relies on a rendezvous with thalamic projections. Neuron. 2013;77:472-84 pubmed publisher
    ..Our study reveals that temporal control of axonal progression contributes to spatial pathfinding of cortical projections and opens perspectives on brain wiring. ..
  51. Fukushima Y, Okada M, Kataoka H, Hirashima M, Yoshida Y, Mann F, et al. Sema3E-PlexinD1 signaling selectively suppresses disoriented angiogenesis in ischemic retinopathy in mice. J Clin Invest. 2011;121:1974-85 pubmed publisher
    ..Our study suggests a new paradigm for vascular regeneration therapy that guides angiogenesis precisely toward the ischemic retina. ..
  52. Sampath H, Batra A, Vartanian V, Carmical J, Prusak D, King I, et al. Variable penetrance of metabolic phenotypes and development of high-fat diet-induced adiposity in NEIL1-deficient mice. Am J Physiol Endocrinol Metab. 2011;300:E724-34 pubmed publisher
    ..Collectively, these data indicate that NEIL1 deficiency results in an increased susceptibility to obesity and related complications potentially by lowering the threshold for tolerance of cellular oxidative stress in neil1(-/-) mice. ..