Plexin-B1 plays a redundant role during mouse development and in tumour angiogenesis
Open accessAbstract
Background: Plexins are a large family of transmembrane receptors for the Semaphorins, known for their role in the assembly of neural circuitry. More recently, Plexins have been implicated in diverse biological functions, including vascular growth, epithelial tissue morphogenesis and tumour development. In particular, PlexinB1, the receptor for Sema4D, has been suggested to play a role in neural development and in tumour angiogenesis, based on in vitro studies. However, the tissue distribution of PlexinB1 has not been extensively studied and the functional relevance of this receptor in vivo still awaits experimental testing. In order to shed light on PlexinB1 function in vivo, we therefore undertook the genomic targeting of the mouse gene to obtain loss of function mutants. Results: This study shows that PlexinB1 receptor and its putative ligand, Sema4D, have a selective distribution in nervous and epithelial tissues during development and in the adult. PlexinB1 and Sema4D show largely complementary cell distribution in tissues, consistent with the idea that PlexinB1 acts as the receptor for Sema4D in vivo. Interestingly, PlexinB1 is also expressed in certain tissues in the absence of Sema4D, suggesting Sema4D independent activities. High expression of PlexinB1 was found in lung, kidney, liver and cerebellum. Mutant mice lacking expression of semaphorin receptor PlexinB1 are viable and fertile. Although the axon collapsing activity of Sema4D is impaired in PlexinB1 deficient neurons, we could not detect major defects in development, or in adult histology and basic functional parameters of tissues expressing PlexinB1. Moreover, in the absence of PlexinB1 the angiogenic response induced by orthotopically implanted tumours was not affected, suggesting that the expression of this semaphorin receptor in endothelial cells is redundant. Conclusion: Our expression analysis suggests a multifaceted role of PlexinB1 during mouse development and tissue homeostasis in the adult. Nonetheless, the genetic deletion of PlexinB1 does not result in major developmental defects or clear functional abnormalities. We infer that PlexinB1 plays a redundant role in mouse development and it is not strictly required for tumour induced angiogenesis.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Plexin-B1 knockout mice are viable and fertile, with no overt neurodevelopmental defects.
“Plexin-B1 knockout (KO) mice are viable and fertile, with no overt neurodevelopmental defects21, 22.”
From Regulation of cell distancing in peri-plaque glial nets by Plexin-B1 affects glial activation and amyloid compaction in Alzheimer’s disease (2024) · cites this paper as [22]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
No citation lists for this paper
No citation lists for this paper yet — checked again daily.
References 41 · Cited by 85
Research works printed but not linked: 41
- Tamagnone L Artigiani S Chen H He Z Ming GI Song H Plexins are a large family of receptors for transmembrane, secreted, and GPI-anchored semaphorins in vertebrates Cell 1999 99 71 80 10520995 10.1016/S0092-8674(00)80063-X · DOI
- Artigiani S Comoglio PM Tamagnone L Plexins, semaphorins, and scatter factor receptors: a common root for cell guidance signals? IUBMB Life 1999 48 477 482 10637762 10.1080/152165499306568 · DOI
- Huber AB Kolodkin AL Ginty DD Cloutier JF Signaling at the growth cone: ligand-receptor complexes and the control of axon growth and guidance Annu Rev Neurosci 2003 26 509 563 12677003 10.1146/annurev.neuro.26.010302.081139 · DOI
- Trusolino L Comoglio PM Scatter-factor and semaphorin receptors: cell signalling for invasive growth Nat Rev Cancer 2002 2 289 300 12001990 10.1038/nrc779 · DOI
- Vikis HG Li W He Z Guan KL The semaphorin receptor plexin-B1 specifically interacts with active Rac in a ligand-dependent manner Proc Natl Acad Sci USA 2000 97 12457 12462 11035813 10.1073/pnas.220421797 PMC18785 · DOI
- Hu H Marton TF Goodman CS Plexin B mediates axon guidance in Drosophila by simultaneously inhibiting active Rac and enhancing RhoA signaling Neuron 2001 32 39 51 11604137 10.1016/S0896-6273(01)00453-6 · DOI
- Driessens MH Hu H Nobes CD Self A Jordens I Goodman CS Plexin-B semaphorin receptors interact directly with active Rac and regulate the actin cytoskeleton by activating Rho Curr Biol 2001 11 339 344 11267870 10.1016/S0960-9822(01)00092-6 · DOI
- Barberis D Casazza A Sordella R Corso S Artigiani S Settleman J p190 Rho-GTPase activating protein associates with plexins and it is required for semaphorin signalling J Cell Sci 2005 118 4689 4700 16188938 10.1242/jcs.02590 · DOI
- Oinuma I Ishikawa Y Katoh H Negishi M The Semaphorin 4D receptor Plexin-B1 is a GTPase activating protein for R-Ras Science 2004 305 862 865 15297673 10.1126/science.1097545 · DOI
- Ito Y Oinuma I Katoh H Kaibuchi K Negishi M Sema4D/plexin-B1 activates GSK-3beta through R-Ras GAP activity, inducing growth cone collapse EMBO Rep 2006 7 704 709 16799460 10.1038/sj.embor.7400737 PMC1500830 · DOI
- Aurandt J Li W Guan KL Semaphorin 4D activates the MAPK pathway downstream of plexin-B1 Biochem J 2005 PMC1408676 16187944
- Basile JR Afkhami T Gutkind JS Semaphorin 4D/plexin-B1 induces endothelial cell migration through the activation of PYK2, Src, and the phosphatidylinositol 3-kinase-Akt pathway Mol Cell Biol 2005 25 6889 6898 16055703 10.1128/MCB.25.16.6889-6898.2005 PMC1190270 · DOI
- Giordano S Corso S Conrotto P Artigiani S Gilestro G Barberis D The semaphorin 4D receptor controls invasive growth by coupling with Met Nat Cell Biol 2002 4 720 724 12198496 10.1038/ncb843 · DOI
- Swiercz JM Kuner R Offermanns S Plexin-B1/RhoGEF-mediated RhoA activation involves the receptor tyrosine kinase ErbB-2 J Cell Biol 2004 165 869 880 15210733 10.1083/jcb.200312094 PMC2172401 · DOI
- Swiercz JM Kuner R Behrens J Offermanns S Plexin-B1 directly interacts with PDZ-RhoGEF/LARG to regulate RhoA and growth cone morphology Neuron 2002 35 51 63 12123608 10.1016/S0896-6273(02)00750-X · DOI
- Conrotto P Valdembri D Corso S Serini G Tamagnone L Comoglio PM Sema4D induces angiogenesis through Met recruitment by Plexin B1 Blood 2005 105 4321 4329 15632204 10.1182/blood-2004-07-2885 · DOI
- Basile JR Barac A Zhu T Guan KL Gutkind JS Class IV semaphorins promote angiogenesis by stimulating Rho-initiated pathways through plexin-B Cancer Res 2004 64 5212 5224 15289326 10.1158/0008-5472.CAN-04-0126 · DOI
- Basile JR Castilho RM Williams VP Gutkind JS Semaphorin 4D provides a link between axon guidance processes and tumor-induced angiogenesis Proc Natl Acad Sci USA 2006 103 9017 9022 16754882 10.1073/pnas.0508825103 PMC1482558 · DOI
- Worzfeld T Puschel AW Offermanns S Kuner R Plexin-B family members demonstrate non-redundant expression patterns in the developing mouse nervous system: an anatomical basis for morphogenetic effects of Sema4D during development Eur J Neurosci 2004 19 2622 2632 15147296 10.1111/j.0953-816X.2004.03401.x · DOI
- Perala NM Immonen T Sariola H The expression of plexins during mouse embryogenesis Gene Expr Patterns 2005 5 355 362 15661641 10.1016/j.modgep.2004.10.001 · DOI
- Moreau-Fauvarque C Kumanogoh A Camand E Jaillard C Barbin G Boquet I The transmembrane semaphorin Sema4D/CD100, an inhibitor of axonal growth, is expressed on oligodendrocytes and upregulated after CNS lesion J Neurosci 2003 23 9229 9239 14534257 PMC6740837
- Kagoshima M Ito T Diverse gene expression and function of semaphorins in developing lung: positive and negative regulatory roles of semaphorins in lung branching morphogenesis Genes Cells 2001 6 559 571 11442635 10.1046/j.1365-2443.2001.00441.x · DOI
- Rossi F Gianola S Corvetti L The strange case of Purkinje axon regeneration and plasticity Cerebellum 2006 5 174 182 16818392 10.1080/14734220600786444 · DOI
- Villegas G Tufro A Ontogeny of semaphorins 3A and 3F and their receptors neuropilins 1 and 2 in the kidney Mech Dev 2002 119 S149 S153 14516677 10.1016/S0925-4773(03)00108-4 · DOI
- Ohmichi H Koshimizu U Matsumoto K Nakamura T Hepatocyte growth factor (HGF) acts as a mesenchyme-derived morphogenic factor during fetal lung development Development 1998 125 1315 1324 9477330
- Masuda K Furuyama T Takahara M Fujioka S Kurinami H Inagaki S Sema4D stimulates axonal outgrowth of embryonic DRG sensory neurones Genes Cells 2004 9 821 829 15330859 10.1111/j.1365-2443.2004.00766.x · DOI
- Behar O Golden JA Mashimo H Schoen FJ Fishman MC Semaphorin III is needed for normal patterning and growth of nerves, bones and heart Nature 1996 383 525 528 8849723 10.1038/383525a0 · DOI
- Sahay A Molliver ME Ginty DD Kolodkin AL Semaphorin 3F is critical for development of limbic system circuitry and is required in neurons for selective CNS axon guidance events J Neurosci 2003 23 6671 6680 12890759 PMC6740712
- Takegahara N Takamatsu H Toyofuku T Tsujimura T Okuno T Yukawa K Plexin-A1 and its interaction with DAP12 in immune responses and bone homeostasis Nat Cell Biol 2006 8 615 622 16715077 10.1038/ncb1416 · DOI
- Ito T Kagoshima M Sasaki Y Li C Udaka N Kitsukawa T Repulsive axon guidance molecule Sema3A inhibits branching morphogenesis of fetal mouse lung Mech Dev 2000 97 35 45 11025205 10.1016/S0925-4773(00)00401-9 · DOI
- Hinck L The versatile roles of "axon guidance" cues in tissue morphogenesis Dev Cell 2004 7 783 793 15572123 10.1016/j.devcel.2004.11.002 · DOI
- Ohta K Mizutani A Kawakami A Murakami Y Kasuya Y Takagi S Plexin: a novel neuronal cell surface molecule that mediates cell adhesion via a homophilic binding mechanism in the presence of calcium ions Neuron 1995 14 1189 1199 7605632 10.1016/0896-6273(95)90266-X · DOI
- Hartwig C Veske A Krejcova S Rosenberger G Finckh U Plexin B3 promotes neurite outgrowth, interacts homophilically, and interacts with Rin BMC Neurosci 2005 6 53 16122393 10.1186/1471-2202-6-53 PMC1215486 · DOI · Paper page
- Artigiani S Conrotto P Fazzari P Gilestro GF Barberis D Giordano S Comoglio PM Tamagnone L Plexin-B3 is a functional receptor for semaphorin 5A EMBO Rep 2004 5 710 4 15218527 10.1038/sj.embor.7400189 PMC1299100 · DOI
- Sotelo C Cellular and genetic regulation of the development of the cerebellar system Prog Neurobiol 2004 72 295 339 15157725 10.1016/j.pneurobio.2004.03.004 · DOI
- Shi W Kumanogoh A Watanabe C Uchida J Wang X Yasui T The class IV semaphorin CD100 plays nonredundant roles in the immune system: defective B and T cell activation in CD100-deficient mice Immunity 2000 13 633 642 11114376 10.1016/S1074-7613(00)00063-7 · DOI
- Corvetti L Rossi F Degradation of chondroitin sulfate proteoglycans induces sprouting of intact purkinje axons in the cerebellum of the adult rat J Neurosci 2005 25 7150 7158 16079397 10.1523/JNEUROSCI.0683-05.2005 PMC6725229 · DOI · Paper page
- Artigiani S Barberis D Fazzari P Longati P Angelini P Van De Loo JW Comoglio PM Tamagnone L Functional regulation of semaphorin receptors by proprotein convertases J Biol Chem 2003 278 10094 101 12533544 10.1074/jbc.M210156200 · DOI
- Dityatev A Dityateva G Schachner M Synaptic strength as a function of post- versus presynaptic expression of the neural cell adhesion molecule NCAM Neuron 2000 26 207 217 10798405 10.1016/S0896-6273(00)81151-4 · DOI
- Barberis D Artigiani S Casazza A Corso S Giordano S Love CA Plexin signaling hampers integrin-based adhesion, leading to Rho-kinase independent cell rounding, and inhibiting lamellipodia extension and cell motility FASEB J 2004 18 592 594 14734633
- Michieli P Mazzone M Basilico C Cavassa S Sottile A Naldini L Targeting the tumor and its microenvironment by a dual-function decoy Met receptor Cancer Cell 2004 6 61 73 15261142 10.1016/j.ccr.2004.05.032 · DOI
- Authors
- Fazzari, P., Penachioni, J., Gianola, S., Rossi, F., Eickholt, B. J., Maina, F., Alexopoulou, L., Sottile, A., Comoglio, P. M., Flavell, R. A., & Tamagnone, L.
- Affiliations
- Candiolo Cancer Institute (IT)
- University of Turin (IT)
- King's College London (GB)
- Centre National de la Recherche Scientifique (FR)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Tamagnone, Luca
- ORCID
- Venue
- BMC Developmental Biology
- Published
- 2007-05-22
- Volume
- 7
- Issue
- 1
- Pages
- 55-55
- ISSN
- 1471-213X (ISSN-L)
- PMC
- PMC1890291
- OpenAlex
- W2088673935
- Cited by
- 85
- References
- 41
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 4 · 2023: 4 · 2022: 2 · 2021: 2 · 2020: 5 · 2019: 3 · 2018: 1 · 2017: 4 · 2016: 4 · 2015: 2 · 2014: 6 · 2013: 4 · 2012: 7
- FWCI
- 3.17
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- Locations
- BMC Developmental Biology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Institutional Research Information System University of Turin (University of Turin) (submittedVersion)
- HAL (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- Associazione Italiana per la Ricerca sul Cancro
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Axon Guidance and Neuronal Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- Sema4D, semaphorin receptors, tumor angiogenesis, mouse development, loss-of-function mutants, tissue distribution, axon guidance, endothelial cells, neural development, tissue homeostasis
- MeSH terms
- Animals, Cells, Cultured, Cerebellum, Embryo, Mammalian, Hippocampus, Immunohistochemistry, Melanoma, Experimental, Mice, Mutant Strains, Morphogenesis, Neovascularization, Pathologic, Nerve Tissue Proteins, Organ Specificity, Receptors, Cell Surface, Tissue Distribution, Gene Expression Regulation, Developmental, Semaphorins, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
