Podoplanin and CLEC-2 drive cerebrovascular patterning and integrity during development
Identifieur interne : 000253 ( Pmc/Curation ); précédent : 000252; suivant : 000254Podoplanin and CLEC-2 drive cerebrovascular patterning and integrity during development
Auteurs : Kate L. Lowe [Royaume-Uni] ; Brenda A. Finney [Royaume-Uni] ; Carsten Deppermann [Allemagne] ; René H Gerling [Allemagne] ; Salomé L. Gazit [France] ; Jon Frampton ; Christopher Buckley [Royaume-Uni] ; Eric Camerer [France] ; Bernhard Nieswandt [Allemagne] ; Friedemann Kiefer [Allemagne] ; Steve P. Watson [Royaume-Uni]Source :
- Blood [ 0006-4971 ] ; 2015.
Abstract
Podoplanin and CLEC-2 critically drive the formation and integrity of developing cerebral blood vessels. Loss of cerebrovascular integrity is influenced by the loss of αIIb-mediated platelet aggregation and platelet secretion.
Url:
DOI: 10.1182/blood-2014-09-603803
PubMed: 25908104
PubMed Central: 4463737
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Gazit</name><affiliation wicri:level="1"><nlm:aff id="aff4">INSERM U970, Paris Cardiovascular Research Centre, Paris, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>INSERM U970, Paris Cardiovascular Research Centre, Paris</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff5">Université Paris-Descartes, Paris, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Université Paris-Descartes, Paris</wicri:regionArea></affiliation></author><author><name sortKey="Frampton, Jon" sort="Frampton, Jon" uniqKey="Frampton J" first="Jon" last="Frampton">Jon Frampton</name><affiliation><nlm:aff wicri:cut=", and" id="aff6">School of Immunity and Infection</nlm:aff></affiliation></author><author><name sortKey="Buckley, Christopher" sort="Buckley, Christopher" uniqKey="Buckley C" first="Christopher" last="Buckley">Christopher Buckley</name><affiliation wicri:level="1"><nlm:aff id="aff7">Rheumatology Research Group, Institute for Biomedical Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Rheumatology Research Group, Institute for Biomedical Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham</wicri:regionArea></affiliation></author><author><name sortKey="Camerer, Eric" sort="Camerer, Eric" uniqKey="Camerer E" first="Eric" last="Camerer">Eric Camerer</name><affiliation wicri:level="1"><nlm:aff id="aff4">INSERM U970, Paris Cardiovascular Research Centre, Paris, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>INSERM U970, Paris Cardiovascular Research Centre, Paris</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff5">Université Paris-Descartes, Paris, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Université Paris-Descartes, Paris</wicri:regionArea></affiliation></author><author><name sortKey="Nieswandt, Bernhard" sort="Nieswandt, Bernhard" uniqKey="Nieswandt B" first="Bernhard" last="Nieswandt">Bernhard Nieswandt</name><affiliation wicri:level="1"><nlm:aff id="aff2">Department of Experimental Biomedicine, University of Würzburg, University Hospital and Rudolf Virchow Centre, Würzburg, Germany;</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Experimental Biomedicine, University of Würzburg, University Hospital and Rudolf Virchow Centre, Würzburg</wicri:regionArea></affiliation></author><author><name sortKey="Kiefer, Friedemann" sort="Kiefer, Friedemann" uniqKey="Kiefer F" first="Friedemann" last="Kiefer">Friedemann Kiefer</name><affiliation wicri:level="1"><nlm:aff id="aff3">Max-Planck-Institute for Molecular Biomedicine, Department Vascular Cell Biology, Münster, Germany;</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Max-Planck-Institute for Molecular Biomedicine, Department Vascular Cell Biology, Münster</wicri:regionArea></affiliation></author><author><name sortKey="Watson, Steve P" sort="Watson, Steve P" uniqKey="Watson S" first="Steve P." last="Watson">Steve P. 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Lowe</name><affiliation wicri:level="1"><nlm:aff id="aff1">Centre for Cardiovascular Sciences, Institute for Biomedical Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom;</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Centre for Cardiovascular Sciences, Institute for Biomedical Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham</wicri:regionArea></affiliation></author><author><name sortKey="Finney, Brenda A" sort="Finney, Brenda A" uniqKey="Finney B" first="Brenda A." last="Finney">Brenda A. Finney</name><affiliation wicri:level="1"><nlm:aff id="aff1">Centre for Cardiovascular Sciences, Institute for Biomedical Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom;</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Centre for Cardiovascular Sciences, Institute for Biomedical Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham</wicri:regionArea></affiliation></author><author><name sortKey="Deppermann, Carsten" sort="Deppermann, Carsten" uniqKey="Deppermann C" first="Carsten" last="Deppermann">Carsten Deppermann</name><affiliation wicri:level="1"><nlm:aff id="aff2">Department of Experimental Biomedicine, University of Würzburg, University Hospital and Rudolf Virchow Centre, Würzburg, Germany;</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Experimental Biomedicine, University of Würzburg, University Hospital and Rudolf Virchow Centre, Würzburg</wicri:regionArea></affiliation></author><author><name sortKey="H Gerling, Rene" sort="H Gerling, Rene" uniqKey="H Gerling R" first="René" last="H Gerling">René H Gerling</name><affiliation wicri:level="1"><nlm:aff id="aff3">Max-Planck-Institute for Molecular Biomedicine, Department Vascular Cell Biology, Münster, Germany;</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Max-Planck-Institute for Molecular Biomedicine, Department Vascular Cell Biology, Münster</wicri:regionArea></affiliation></author><author><name sortKey="Gazit, Salome L" sort="Gazit, Salome L" uniqKey="Gazit S" first="Salomé L." last="Gazit">Salomé L. Gazit</name><affiliation wicri:level="1"><nlm:aff id="aff4">INSERM U970, Paris Cardiovascular Research Centre, Paris, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>INSERM U970, Paris Cardiovascular Research Centre, Paris</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff5">Université Paris-Descartes, Paris, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Université Paris-Descartes, Paris</wicri:regionArea></affiliation></author><author><name sortKey="Frampton, Jon" sort="Frampton, Jon" uniqKey="Frampton J" first="Jon" last="Frampton">Jon Frampton</name><affiliation><nlm:aff wicri:cut=", and" id="aff6">School of Immunity and Infection</nlm:aff></affiliation></author><author><name sortKey="Buckley, Christopher" sort="Buckley, Christopher" uniqKey="Buckley C" first="Christopher" last="Buckley">Christopher Buckley</name><affiliation wicri:level="1"><nlm:aff id="aff7">Rheumatology Research Group, Institute for Biomedical Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Rheumatology Research Group, Institute for Biomedical Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham</wicri:regionArea></affiliation></author><author><name sortKey="Camerer, Eric" sort="Camerer, Eric" uniqKey="Camerer E" first="Eric" last="Camerer">Eric Camerer</name><affiliation wicri:level="1"><nlm:aff id="aff4">INSERM U970, Paris Cardiovascular Research Centre, Paris, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>INSERM U970, Paris Cardiovascular Research Centre, Paris</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff5">Université Paris-Descartes, Paris, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Université Paris-Descartes, Paris</wicri:regionArea></affiliation></author><author><name sortKey="Nieswandt, Bernhard" sort="Nieswandt, Bernhard" uniqKey="Nieswandt B" first="Bernhard" last="Nieswandt">Bernhard Nieswandt</name><affiliation wicri:level="1"><nlm:aff id="aff2">Department of Experimental Biomedicine, University of Würzburg, University Hospital and Rudolf Virchow Centre, Würzburg, Germany;</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Experimental Biomedicine, University of Würzburg, University Hospital and Rudolf Virchow Centre, Würzburg</wicri:regionArea></affiliation></author><author><name sortKey="Kiefer, Friedemann" sort="Kiefer, Friedemann" uniqKey="Kiefer F" first="Friedemann" last="Kiefer">Friedemann Kiefer</name><affiliation wicri:level="1"><nlm:aff id="aff3">Max-Planck-Institute for Molecular Biomedicine, Department Vascular Cell Biology, Münster, Germany;</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Max-Planck-Institute for Molecular Biomedicine, Department Vascular Cell Biology, Münster</wicri:regionArea></affiliation></author><author><name sortKey="Watson, Steve P" sort="Watson, Steve P" uniqKey="Watson S" first="Steve P." last="Watson">Steve P. Watson</name><affiliation wicri:level="1"><nlm:aff id="aff1">Centre for Cardiovascular Sciences, Institute for Biomedical Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom;</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Centre for Cardiovascular Sciences, Institute for Biomedical Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham</wicri:regionArea></affiliation></author></analytic><series><title level="j">Blood</title><idno type="ISSN">0006-4971</idno><idno type="eISSN">1528-0020</idno><imprint><date when="2015">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><title>Key Points</title><p><list list-type="bullet"><list-item><p>Podoplanin and CLEC-2 critically drive the formation and integrity of developing cerebral blood vessels.</p></list-item><list-item><p>Loss of cerebrovascular integrity is influenced by the loss of αIIb-mediated platelet aggregation and platelet secretion.</p></list-item></list></p></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Blood</journal-id><journal-id journal-id-type="iso-abbrev">Blood</journal-id><journal-id journal-id-type="hwp">bloodjournal</journal-id><journal-id journal-id-type="pmc">blood</journal-id><journal-id journal-id-type="publisher-id">Blood</journal-id><journal-title-group><journal-title>Blood</journal-title></journal-title-group><issn pub-type="ppub">0006-4971</issn><issn pub-type="epub">1528-0020</issn><publisher><publisher-name>American Society of Hematology</publisher-name><publisher-loc>Washington, DC</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">25908104</article-id><article-id pub-id-type="pmc">4463737</article-id><article-id pub-id-type="publisher-id">2014/603803</article-id><article-id pub-id-type="doi">10.1182/blood-2014-09-603803</article-id><article-categories><subj-group subj-group-type="hwp-journal-coll"><subject>35</subject><subject>37</subject><subject>38</subject></subj-group><subj-group subj-group-type="heading"><subject>Platelets and Thrombopoiesis</subject></subj-group></article-categories><title-group><article-title>Podoplanin and CLEC-2 drive cerebrovascular patterning and integrity during development</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Lowe</surname><given-names>Kate L.</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Finney</surname><given-names>Brenda A.</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Deppermann</surname><given-names>Carsten</given-names></name><xref ref-type="aff" rid="aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Hägerling</surname><given-names>René</given-names></name><xref ref-type="aff" rid="aff3">3</xref></contrib><contrib contrib-type="author"><name><surname>Gazit</surname><given-names>Salomé L.</given-names></name><xref ref-type="aff" rid="aff4">4</xref><xref ref-type="aff" rid="aff5">5</xref></contrib><contrib contrib-type="author"><name><surname>Frampton</surname><given-names>Jon</given-names></name><xref ref-type="aff" rid="aff6">6</xref></contrib><contrib contrib-type="author"><name><surname>Buckley</surname><given-names>Christopher</given-names></name><xref ref-type="aff" rid="aff7">7</xref></contrib><contrib contrib-type="author"><name><surname>Camerer</surname><given-names>Eric</given-names></name><xref ref-type="aff" rid="aff4">4</xref><xref ref-type="aff" rid="aff5">5</xref></contrib><contrib contrib-type="author"><name><surname>Nieswandt</surname><given-names>Bernhard</given-names></name><xref ref-type="aff" rid="aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Kiefer</surname><given-names>Friedemann</given-names></name><xref ref-type="aff" rid="aff3">3</xref><contrib-id contrib-id-type="orcid">http://orcid.org/0000-0002-3002-8237</contrib-id></contrib><contrib contrib-type="author" corresp="yes"><name><surname>Watson</surname><given-names>Steve P.</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><aff id="aff1"><label>1</label>Centre for Cardiovascular Sciences, Institute for Biomedical Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom;</aff><aff id="aff2"><label>2</label>Department of Experimental Biomedicine, University of Würzburg, University Hospital and Rudolf Virchow Centre, Würzburg, Germany;</aff><aff id="aff3"><label>3</label>Max-Planck-Institute for Molecular Biomedicine, Department Vascular Cell Biology, Münster, Germany;</aff><aff id="aff4"><label>4</label>INSERM U970, Paris Cardiovascular Research Centre, Paris, France;</aff><aff id="aff5"><label>5</label>Université Paris-Descartes, Paris, France;</aff><aff id="aff6"><label>6</label>School of Immunity and Infection, and</aff><aff id="aff7"><label>7</label>Rheumatology Research Group, Institute for Biomedical Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom</aff></contrib-group><pub-date pub-type="ppub"><day>11</day><month>6</month><year>2015</year></pub-date><pub-date pub-type="epreprint"><day>23</day><month>4</month><year>2015</year></pub-date><pub-date pub-type="pmc-release"><day>11</day><month>6</month><year>2015</year></pub-date><pmc-comment> PMC Release delay is 0 months and 0 days and was based on the
<volume>125</volume><issue>24</issue><fpage>3769</fpage><lpage>3777</lpage><history><date date-type="received"><day>29</day><month>9</month><year>2014</year></date><date date-type="accepted"><day>15</day><month>4</month><year>2015</year></date></history><permissions><copyright-statement>© 2015 by The American Society of Hematology</copyright-statement><copyright-year>2015</copyright-year></permissions><self-uri xlink:title="pdf" xlink:type="simple" xlink:href="3769.pdf"></self-uri><abstract abstract-type="executive-summary"><title>Key Points</title><p><list list-type="bullet"><list-item><p>Podoplanin and CLEC-2 critically drive the formation and integrity of developing cerebral blood vessels.</p></list-item><list-item><p>Loss of cerebrovascular integrity is influenced by the loss of αIIb-mediated platelet aggregation and platelet secretion.</p></list-item></list></p></abstract><abstract><p>Mice with a constitutive or platelet-specific deletion of the C-type-lectin-like receptor (CLEC-2) exhibit hemorrhaging in the brain at mid-gestation. We sought to investigate the basis of this defect, hypothesizing that it is mediated by the loss of CLEC-2 activation by its endogenous ligand, podoplanin, which is expressed on the developing neural tube. To induce deletion of podoplanin at the 2-cell stage, we generated a <italic>podoplanin</italic><sup><italic>fl/fl</italic></sup> mouse crossed to a PGK-Cre mouse. Using 3-dimensional light-sheet microscopy, we observed cerebral vessels were tortuous and aberrantly patterned at embryonic (E) day 10.5 in podoplanin- and CLEC-2-deficient mice, preceding the formation of large hemorrhages throughout the fore-, mid-, and hindbrain by E11.5. Immunofluorescence and electron microscopy revealed defective pericyte recruitment and misconnections between the endothelium of developing blood vessels and surrounding pericytes and neuro-epithelial cells. Nestin-Cre-driven deletion of podoplanin on neural progenitors also caused widespread cerebral hemorrhaging. Hemorrhaging was also seen in the ventricles of embryos deficient in the platelet integrin subunit glycoprotein IIb or in embryos in which platelet α-granule and dense granule secretion is abolished. We propose a novel role for podoplanin on the neuro-epithelium, which interacts with CLEC-2 on platelets, mediating platelet adhesion, aggregation, and secretion to guide the maturation and integrity of the developing vasculature and prevent hemorrhage.</p></abstract><counts><page-count count="9"></page-count></counts><custom-meta-group><custom-meta><meta-name>access</meta-name><meta-value>free</meta-value></custom-meta></custom-meta-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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