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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Semaphorin3A, Neuropilin-1, and PlexinA1 Are Required for Lymphatic Valve Formation</title>
<author><name sortKey="Bouvree, Karine" sort="Bouvree, Karine" uniqKey="Bouvree K" first="Karine" last="Bouvrée">Karine Bouvrée</name>
</author>
<author><name sortKey="Brunet, Isabelle" sort="Brunet, Isabelle" uniqKey="Brunet I" first="Isabelle" last="Brunet">Isabelle Brunet</name>
</author>
<author><name sortKey="Del Toro, Raquel" sort="Del Toro, Raquel" uniqKey="Del Toro R" first="Raquel" last="Del Toro">Raquel Del Toro</name>
</author>
<author><name sortKey="Gordon, Emma" sort="Gordon, Emma" uniqKey="Gordon E" first="Emma" last="Gordon">Emma Gordon</name>
</author>
<author><name sortKey="Prahst, Claudia" sort="Prahst, Claudia" uniqKey="Prahst C" first="Claudia" last="Prahst">Claudia Prahst</name>
</author>
<author><name sortKey="Cristofaro, Brunella" sort="Cristofaro, Brunella" uniqKey="Cristofaro B" first="Brunella" last="Cristofaro">Brunella Cristofaro</name>
</author>
<author><name sortKey="Mathivet, Thomas" sort="Mathivet, Thomas" uniqKey="Mathivet T" first="Thomas" last="Mathivet">Thomas Mathivet</name>
</author>
<author><name sortKey="Xu, Yunling" sort="Xu, Yunling" uniqKey="Xu Y" first="Yunling" last="Xu">Yunling Xu</name>
</author>
<author><name sortKey="Soueid, Jihane" sort="Soueid, Jihane" uniqKey="Soueid J" first="Jihane" last="Soueid">Jihane Soueid</name>
</author>
<author><name sortKey="Fortuna, Vitor" sort="Fortuna, Vitor" uniqKey="Fortuna V" first="Vitor" last="Fortuna">Vitor Fortuna</name>
</author>
<author><name sortKey="Miura, Nayoki" sort="Miura, Nayoki" uniqKey="Miura N" first="Nayoki" last="Miura">Nayoki Miura</name>
</author>
<author><name sortKey="Aigrot, Marie Stephane" sort="Aigrot, Marie Stephane" uniqKey="Aigrot M" first="Marie-Stéphane" last="Aigrot">Marie-Stéphane Aigrot</name>
</author>
<author><name sortKey="Maden, Charlotte H" sort="Maden, Charlotte H" uniqKey="Maden C" first="Charlotte H." last="Maden">Charlotte H. Maden</name>
</author>
<author><name sortKey="Ruhrberg, Christiana" sort="Ruhrberg, Christiana" uniqKey="Ruhrberg C" first="Christiana" last="Ruhrberg">Christiana Ruhrberg</name>
</author>
<author><name sortKey="Thomas, Jean Leon" sort="Thomas, Jean Leon" uniqKey="Thomas J" first="Jean Léon" last="Thomas">Jean Léon Thomas</name>
</author>
<author><name sortKey="Eichmann, Anne" sort="Eichmann, Anne" uniqKey="Eichmann A" first="Anne" last="Eichmann">Anne Eichmann</name>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">22723296</idno>
<idno type="pmc">3861899</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3861899</idno>
<idno type="RBID">PMC:3861899</idno>
<idno type="doi">10.1161/CIRCRESAHA.112.269316</idno>
<date when="2012">2012</date>
<idno type="wicri:Area/Pmc/Corpus">003236</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">003236</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Semaphorin3A, Neuropilin-1, and PlexinA1 Are Required for Lymphatic Valve Formation</title>
<author><name sortKey="Bouvree, Karine" sort="Bouvree, Karine" uniqKey="Bouvree K" first="Karine" last="Bouvrée">Karine Bouvrée</name>
</author>
<author><name sortKey="Brunet, Isabelle" sort="Brunet, Isabelle" uniqKey="Brunet I" first="Isabelle" last="Brunet">Isabelle Brunet</name>
</author>
<author><name sortKey="Del Toro, Raquel" sort="Del Toro, Raquel" uniqKey="Del Toro R" first="Raquel" last="Del Toro">Raquel Del Toro</name>
</author>
<author><name sortKey="Gordon, Emma" sort="Gordon, Emma" uniqKey="Gordon E" first="Emma" last="Gordon">Emma Gordon</name>
</author>
<author><name sortKey="Prahst, Claudia" sort="Prahst, Claudia" uniqKey="Prahst C" first="Claudia" last="Prahst">Claudia Prahst</name>
</author>
<author><name sortKey="Cristofaro, Brunella" sort="Cristofaro, Brunella" uniqKey="Cristofaro B" first="Brunella" last="Cristofaro">Brunella Cristofaro</name>
</author>
<author><name sortKey="Mathivet, Thomas" sort="Mathivet, Thomas" uniqKey="Mathivet T" first="Thomas" last="Mathivet">Thomas Mathivet</name>
</author>
<author><name sortKey="Xu, Yunling" sort="Xu, Yunling" uniqKey="Xu Y" first="Yunling" last="Xu">Yunling Xu</name>
</author>
<author><name sortKey="Soueid, Jihane" sort="Soueid, Jihane" uniqKey="Soueid J" first="Jihane" last="Soueid">Jihane Soueid</name>
</author>
<author><name sortKey="Fortuna, Vitor" sort="Fortuna, Vitor" uniqKey="Fortuna V" first="Vitor" last="Fortuna">Vitor Fortuna</name>
</author>
<author><name sortKey="Miura, Nayoki" sort="Miura, Nayoki" uniqKey="Miura N" first="Nayoki" last="Miura">Nayoki Miura</name>
</author>
<author><name sortKey="Aigrot, Marie Stephane" sort="Aigrot, Marie Stephane" uniqKey="Aigrot M" first="Marie-Stéphane" last="Aigrot">Marie-Stéphane Aigrot</name>
</author>
<author><name sortKey="Maden, Charlotte H" sort="Maden, Charlotte H" uniqKey="Maden C" first="Charlotte H." last="Maden">Charlotte H. Maden</name>
</author>
<author><name sortKey="Ruhrberg, Christiana" sort="Ruhrberg, Christiana" uniqKey="Ruhrberg C" first="Christiana" last="Ruhrberg">Christiana Ruhrberg</name>
</author>
<author><name sortKey="Thomas, Jean Leon" sort="Thomas, Jean Leon" uniqKey="Thomas J" first="Jean Léon" last="Thomas">Jean Léon Thomas</name>
</author>
<author><name sortKey="Eichmann, Anne" sort="Eichmann, Anne" uniqKey="Eichmann A" first="Anne" last="Eichmann">Anne Eichmann</name>
</author>
</analytic>
<series><title level="j">Circulation research</title>
<idno type="ISSN">0009-7330</idno>
<idno type="eISSN">1524-4571</idno>
<imprint><date when="2012">2012</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><sec id="S1"><title>Rationale</title>
<p id="P1">The lymphatic vasculature plays a major role in fluid homeostasis, absorption of dietary lipids, and immune surveillance. Fluid transport depends on the presence of intraluminal valves within lymphatic collectors. Defective formation of lymphatic valves leads to lymphedema, a progressive and debilitating condition for which curative treatments are currently unavailable. How lymphatic valve formation is regulated remains largely unknown.</p>
</sec>
<sec id="S2"><title>Objective</title>
<p id="P2">We investigated if the repulsive axon guidance molecule Semaphorin3A (Sema3A) plays a role in lymphatic valve formation.</p>
</sec>
<sec id="S3"><title>Methods and Results</title>
<p id="P3">We show that Sema3A mRNA is expressed in lymphatic vessels and that Sema3A protein binds to lymphatic valves expressing the Neuropilin-1 (Nrp1) and PlexinA1 receptors. Using mouse knockout models, we show that Sema3A is selectively required for lymphatic valve formation, via interaction with Nrp1 and PlexinA1. Sema3a<sup>−/−</sup>
mice exhibit defects in lymphatic valve formation, which are not due to abnormal lymphatic patterning or sprouting, and mice carrying a mutation in the Sema3A binding site of Nrp1, or deficient for Plxna1, develop lymphatic valve defects similar to those seen in Sema3a<sup>−/−</sup>
mice.</p>
</sec>
<sec id="S4"><title>Conclusions</title>
<p id="P4">Our data demonstrate an essential direct function of Sema3A-Nrp1-PlexinA1 signaling in lymphatic valve formation.</p>
</sec>
</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>
<pmc-dir>properties manuscript</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-journal-id">0047103</journal-id>
<journal-id journal-id-type="pubmed-jr-id">2974</journal-id>
<journal-id journal-id-type="nlm-ta">Circ Res</journal-id>
<journal-id journal-id-type="iso-abbrev">Circ. Res.</journal-id>
<journal-title-group><journal-title>Circulation research</journal-title>
</journal-title-group>
<issn pub-type="ppub">0009-7330</issn>
<issn pub-type="epub">1524-4571</issn>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">22723296</article-id>
<article-id pub-id-type="pmc">3861899</article-id>
<article-id pub-id-type="doi">10.1161/CIRCRESAHA.112.269316</article-id>
<article-id pub-id-type="manuscript">NIHMS419298</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Article</subject>
</subj-group>
</article-categories>
<title-group><article-title>Semaphorin3A, Neuropilin-1, and PlexinA1 Are Required for Lymphatic Valve Formation</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Bouvrée</surname>
<given-names>Karine</given-names>
</name>
<xref rid="FN2" ref-type="author-notes">*</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Brunet</surname>
<given-names>Isabelle</given-names>
</name>
<xref rid="FN2" ref-type="author-notes">*</xref>
</contrib>
<contrib contrib-type="author"><name><surname>del Toro</surname>
<given-names>Raquel</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Gordon</surname>
<given-names>Emma</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Prahst</surname>
<given-names>Claudia</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Cristofaro</surname>
<given-names>Brunella</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Mathivet</surname>
<given-names>Thomas</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Xu</surname>
<given-names>Yunling</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Soueid</surname>
<given-names>Jihane</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Fortuna</surname>
<given-names>Vitor</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Miura</surname>
<given-names>Nayoki</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Aigrot</surname>
<given-names>Marie-Stéphane</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Maden</surname>
<given-names>Charlotte H.</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Ruhrberg</surname>
<given-names>Christiana</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Thomas</surname>
<given-names>Jean Léon</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Eichmann</surname>
<given-names>Anne</given-names>
</name>
</contrib>
<aff id="A1">CIRB Collège de France/CNRS UMR 7241/INSERM U1050, Paris, France (K.B., I.B., R.d.T., B.C., T.M., Y.X., V.F., A.E.); the Department of Cardiology, Yale University School of Medicine, New Haven, CT (E.G., C.P., A.E.); Inserm UMR-S 975, CNRS UMR 7225, UPMC, Hôpital de la Pitié-Salpêtrière, Paris, France (J.S., M.-S.A., J.L.T.); the Department of Biochemistry, Hamamatsu University School of Medicine, Hamamatsu, Japan (N.M.); Institute of Ophthalmology, University College London, London, United Kingdom (C.H.M., C.R.); and the Department of Neurology, Yale University School of Medicine, New Haven, CT (J.L.T.)</aff>
</contrib-group>
<author-notes><corresp id="FN1">Correspondence to: Anne Eichmann, PhD, Department of Cardiology, Yale University School of Medicine, 300 George St, New Haven, CT 06510-3221. <email>anne.eichmann@yale.edu</email>
</corresp>
<fn id="FN2" fn-type="equal"><label>*</label>
<p>These authors contributed equally to this work.</p>
</fn>
</author-notes>
<pub-date pub-type="nihms-submitted"><day>1</day>
<month>12</month>
<year>2013</year>
</pub-date>
<pub-date pub-type="epub"><day>21</day>
<month>6</month>
<year>2012</year>
</pub-date>
<pub-date pub-type="ppub"><day>3</day>
<month>8</month>
<year>2012</year>
</pub-date>
<pub-date pub-type="pmc-release"><day>13</day>
<month>12</month>
<year>2013</year>
</pub-date>
<volume>111</volume>
<issue>4</issue>
<elocation-id>10.1161/CIRCRESAHA.112.269316</elocation-id>
<permissions><copyright-statement>© 2012 American Heart Association, Inc.</copyright-statement>
<copyright-year>2012</copyright-year>
</permissions>
<abstract><sec id="S1"><title>Rationale</title>
<p id="P1">The lymphatic vasculature plays a major role in fluid homeostasis, absorption of dietary lipids, and immune surveillance. Fluid transport depends on the presence of intraluminal valves within lymphatic collectors. Defective formation of lymphatic valves leads to lymphedema, a progressive and debilitating condition for which curative treatments are currently unavailable. How lymphatic valve formation is regulated remains largely unknown.</p>
</sec>
<sec id="S2"><title>Objective</title>
<p id="P2">We investigated if the repulsive axon guidance molecule Semaphorin3A (Sema3A) plays a role in lymphatic valve formation.</p>
</sec>
<sec id="S3"><title>Methods and Results</title>
<p id="P3">We show that Sema3A mRNA is expressed in lymphatic vessels and that Sema3A protein binds to lymphatic valves expressing the Neuropilin-1 (Nrp1) and PlexinA1 receptors. Using mouse knockout models, we show that Sema3A is selectively required for lymphatic valve formation, via interaction with Nrp1 and PlexinA1. Sema3a<sup>−/−</sup>
mice exhibit defects in lymphatic valve formation, which are not due to abnormal lymphatic patterning or sprouting, and mice carrying a mutation in the Sema3A binding site of Nrp1, or deficient for Plxna1, develop lymphatic valve defects similar to those seen in Sema3a<sup>−/−</sup>
mice.</p>
</sec>
<sec id="S4"><title>Conclusions</title>
<p id="P4">Our data demonstrate an essential direct function of Sema3A-Nrp1-PlexinA1 signaling in lymphatic valve formation.</p>
</sec>
</abstract>
<kwd-group><kwd>valve</kwd>
<kwd>guidance</kwd>
<kwd>development</kwd>
<kwd>lymphatic vessel</kwd>
<kwd>vascular biology</kwd>
<kwd>vascular smooth muscle</kwd>
</kwd-group>
<funding-group><award-group><funding-source country="United States">National Heart, Lung, and Blood Institute : NHLBI</funding-source>
<award-id>R01 HL111504 || HL</award-id>
</award-group>
</funding-group>
</article-meta>
</front>
</pmc>
</record>
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