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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">An essential role for <italic>Prox1</italic>
in the induction of the lymphatic endothelial cell phenotype</title>
<author><name sortKey="Wigle, Jeffrey T" sort="Wigle, Jeffrey T" uniqKey="Wigle J" first="Jeffrey T." last="Wigle">Jeffrey T. Wigle</name>
<affiliation><nlm:aff id="N0x99ab270.0x8bcf128">Department of Genetics, St Jude Children’s Research Hospital, Memphis, TN 38105,</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="N0x99ab270.0x8bcf128">Present address: Division of Stroke and Vascular Disease and Department of Biochemistry and Medical Genetics, St Boniface General Hospital Research Centre, Winnipeg, Canada</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Harvey, Natasha" sort="Harvey, Natasha" uniqKey="Harvey N" first="Natasha" last="Harvey">Natasha Harvey</name>
<affiliation><nlm:aff id="N0x99ab270.0x8bcf128">Department of Genetics, St Jude Children’s Research Hospital, Memphis, TN 38105,</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Detmar, Michael" sort="Detmar, Michael" uniqKey="Detmar M" first="Michael" last="Detmar">Michael Detmar</name>
<affiliation><nlm:aff id="N0x99ab270.0x8bcf128">Cutaneous Biology Research Center and Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114,</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Lagutina, Irina" sort="Lagutina, Irina" uniqKey="Lagutina I" first="Irina" last="Lagutina">Irina Lagutina</name>
<affiliation><nlm:aff id="N0x99ab270.0x8bcf128">Department of Genetics, St Jude Children’s Research Hospital, Memphis, TN 38105,</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Grosveld, Gerard" sort="Grosveld, Gerard" uniqKey="Grosveld G" first="Gerard" last="Grosveld">Gerard Grosveld</name>
<affiliation><nlm:aff id="N0x99ab270.0x8bcf128">Department of Genetics, St Jude Children’s Research Hospital, Memphis, TN 38105,</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Gunn, Michael D" sort="Gunn, Michael D" uniqKey="Gunn M" first="Michael D." last="Gunn">Michael D. Gunn</name>
<affiliation><nlm:aff wicri:cut=" and" id="N0x99ab270.0x8bcf128">Division of Cardiology, Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Jackson, David G" sort="Jackson, David G" uniqKey="Jackson D" first="David G." last="Jackson">David G. Jackson</name>
<affiliation><nlm:aff id="N0x99ab270.0x8bcf128">MRC Human Immunology Unit, Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford OX3 9DS, UK</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Oliver, Guillermo" sort="Oliver, Guillermo" uniqKey="Oliver G" first="Guillermo" last="Oliver">Guillermo Oliver</name>
<affiliation><nlm:aff id="N0x99ab270.0x8bcf128">Department of Genetics, St Jude Children’s Research Hospital, Memphis, TN 38105,</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="N0x99ab270.0x8bcf128">Corresponding author e-mail: guillermo.oliver@stjude.org</nlm:aff>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">11927535</idno>
<idno type="pmc">125938</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC125938</idno>
<idno type="RBID">PMC:125938</idno>
<idno type="doi">10.1093/emboj/21.7.1505</idno>
<date when="2002">2002</date>
<idno type="wicri:Area/Pmc/Corpus">001752</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001752</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">An essential role for <italic>Prox1</italic>
in the induction of the lymphatic endothelial cell phenotype</title>
<author><name sortKey="Wigle, Jeffrey T" sort="Wigle, Jeffrey T" uniqKey="Wigle J" first="Jeffrey T." last="Wigle">Jeffrey T. Wigle</name>
<affiliation><nlm:aff id="N0x99ab270.0x8bcf128">Department of Genetics, St Jude Children’s Research Hospital, Memphis, TN 38105,</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="N0x99ab270.0x8bcf128">Present address: Division of Stroke and Vascular Disease and Department of Biochemistry and Medical Genetics, St Boniface General Hospital Research Centre, Winnipeg, Canada</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Harvey, Natasha" sort="Harvey, Natasha" uniqKey="Harvey N" first="Natasha" last="Harvey">Natasha Harvey</name>
<affiliation><nlm:aff id="N0x99ab270.0x8bcf128">Department of Genetics, St Jude Children’s Research Hospital, Memphis, TN 38105,</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Detmar, Michael" sort="Detmar, Michael" uniqKey="Detmar M" first="Michael" last="Detmar">Michael Detmar</name>
<affiliation><nlm:aff id="N0x99ab270.0x8bcf128">Cutaneous Biology Research Center and Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114,</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Lagutina, Irina" sort="Lagutina, Irina" uniqKey="Lagutina I" first="Irina" last="Lagutina">Irina Lagutina</name>
<affiliation><nlm:aff id="N0x99ab270.0x8bcf128">Department of Genetics, St Jude Children’s Research Hospital, Memphis, TN 38105,</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Grosveld, Gerard" sort="Grosveld, Gerard" uniqKey="Grosveld G" first="Gerard" last="Grosveld">Gerard Grosveld</name>
<affiliation><nlm:aff id="N0x99ab270.0x8bcf128">Department of Genetics, St Jude Children’s Research Hospital, Memphis, TN 38105,</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Gunn, Michael D" sort="Gunn, Michael D" uniqKey="Gunn M" first="Michael D." last="Gunn">Michael D. Gunn</name>
<affiliation><nlm:aff wicri:cut=" and" id="N0x99ab270.0x8bcf128">Division of Cardiology, Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Jackson, David G" sort="Jackson, David G" uniqKey="Jackson D" first="David G." last="Jackson">David G. Jackson</name>
<affiliation><nlm:aff id="N0x99ab270.0x8bcf128">MRC Human Immunology Unit, Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford OX3 9DS, UK</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Oliver, Guillermo" sort="Oliver, Guillermo" uniqKey="Oliver G" first="Guillermo" last="Oliver">Guillermo Oliver</name>
<affiliation><nlm:aff id="N0x99ab270.0x8bcf128">Department of Genetics, St Jude Children’s Research Hospital, Memphis, TN 38105,</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="N0x99ab270.0x8bcf128">Corresponding author e-mail: guillermo.oliver@stjude.org</nlm:aff>
</affiliation>
</author>
</analytic>
<series><title level="j">The EMBO Journal</title>
<idno type="ISSN">0261-4189</idno>
<idno type="eISSN">1460-2075</idno>
<imprint><date when="2002">2002</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><p>The process of angiogenesis has been well documented, but little is known about the biology of lymphatic endothelial cells and the molecular mechanisms controlling lymphangiogenesis. The homeobox gene <italic>Prox1</italic>
is expressed in a subpopulation of endothelial cells that, after budding from veins, gives rise to the mammalian lymphatic system. In <italic>Prox1</italic>
<sup>–</sup>
<sup>/–</sup>
embryos, this budding becomes arrested at around embryonic day (E)11.5, resulting in embryos without lymphatic vasculature. Unlike the endothelial cells that bud off in E11.5 wild-type embryos, those of <italic>Prox1</italic>
-null embryos did not co-express any lymphatic markers such as VEGFR-3, LYVE-1 or SLC. Instead, the mutant cells appeared to have a blood vascular phenotype, as determined by their expression of laminin and CD34. These results suggest that <italic>Prox1</italic>
activity is required for both maintenance of the budding of the venous endothelial cells and differentiation toward the lymphatic phenotype. On the basis of our findings, we propose that a blood vascular phenotype is the default fate of budding embryonic venous endothelial cells; upon expression of Prox1, these budding cells adopt a lymphatic vasculature phenotype.</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">EMBO J</journal-id>
<journal-title>The EMBO Journal</journal-title>
<issn pub-type="ppub">0261-4189</issn>
<issn pub-type="epub">1460-2075</issn>
<publisher><publisher-name>Oxford University Press</publisher-name>
<publisher-loc>Oxford, UK</publisher-loc>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">11927535</article-id>
<article-id pub-id-type="pmc">125938</article-id>
<article-id pub-id-type="publisher-id">cdf152</article-id>
<article-id pub-id-type="doi">10.1093/emboj/21.7.1505</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Article</subject>
</subj-group>
</article-categories>
<title-group><article-title>An essential role for <italic>Prox1</italic>
in the induction of the lymphatic endothelial cell phenotype</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Wigle</surname>
<given-names>Jeffrey T.</given-names>
</name>
<xref ref-type="aff" rid="N0x99ab270.0x8bcf128">1</xref>
<xref ref-type="aff" rid="N0x99ab270.0x8bcf128">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Harvey</surname>
<given-names>Natasha</given-names>
</name>
<xref ref-type="aff" rid="N0x99ab270.0x8bcf128">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Detmar</surname>
<given-names>Michael</given-names>
</name>
<xref ref-type="aff" rid="N0x99ab270.0x8bcf128">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Lagutina</surname>
<given-names>Irina</given-names>
</name>
<xref ref-type="aff" rid="N0x99ab270.0x8bcf128">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Grosveld</surname>
<given-names>Gerard</given-names>
</name>
<xref ref-type="aff" rid="N0x99ab270.0x8bcf128">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Gunn</surname>
<given-names>Michael D.</given-names>
</name>
<xref ref-type="aff" rid="N0x99ab270.0x8bcf128">4</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Jackson</surname>
<given-names>David G.</given-names>
</name>
<xref ref-type="aff" rid="N0x99ab270.0x8bcf128">5</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Oliver</surname>
<given-names>Guillermo</given-names>
</name>
<xref ref-type="aff" rid="N0x99ab270.0x8bcf128">1</xref>
<xref ref-type="aff" rid="N0x99ab270.0x8bcf128">6</xref>
</contrib>
</contrib-group>
<aff id="N0x99ab270.0x8bcf128"><label>1</label>
Department of Genetics, St Jude Children’s Research Hospital, Memphis, TN 38105,<label>3</label>
Cutaneous Biology Research Center and Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114,<label>4</label>
Division of Cardiology, Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA and<label>5</label>
MRC Human Immunology Unit, Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford OX3 9DS, UK<label>2</label>
Present address: Division of Stroke and Vascular Disease and Department of Biochemistry and Medical Genetics, St Boniface General Hospital Research Centre, Winnipeg, Canada<label>6</label>
Corresponding author e-mail: guillermo.oliver@stjude.org</aff>
<pub-date pub-type="ppub"><day>2</day>
<month>4</month>
<year>2002</year>
</pub-date>
<volume>21</volume>
<issue>7</issue>
<fpage>1505</fpage>
<lpage>1513</lpage>
<ext-link ext-link-type="uri" xlink:href="http://www.emboj.oupjournals.org/content/vol21/issue7/"></ext-link>
<history><date date-type="received"><day>17</day>
<month>12</month>
<year>2001</year>
</date>
<date date-type="rev-recd"><day>22</day>
<month>1</month>
<year>2002</year>
</date>
<date date-type="accepted"><day>31</day>
<month>1</month>
<year>2002</year>
</date>
</history>
<copyright-statement>Copyright © 2002 European Molecular Biology Organization</copyright-statement>
<copyright-year>2002</copyright-year>
<abstract><p>The process of angiogenesis has been well documented, but little is known about the biology of lymphatic endothelial cells and the molecular mechanisms controlling lymphangiogenesis. The homeobox gene <italic>Prox1</italic>
is expressed in a subpopulation of endothelial cells that, after budding from veins, gives rise to the mammalian lymphatic system. In <italic>Prox1</italic>
<sup>–</sup>
<sup>/–</sup>
embryos, this budding becomes arrested at around embryonic day (E)11.5, resulting in embryos without lymphatic vasculature. Unlike the endothelial cells that bud off in E11.5 wild-type embryos, those of <italic>Prox1</italic>
-null embryos did not co-express any lymphatic markers such as VEGFR-3, LYVE-1 or SLC. Instead, the mutant cells appeared to have a blood vascular phenotype, as determined by their expression of laminin and CD34. These results suggest that <italic>Prox1</italic>
activity is required for both maintenance of the budding of the venous endothelial cells and differentiation toward the lymphatic phenotype. On the basis of our findings, we propose that a blood vascular phenotype is the default fate of budding embryonic venous endothelial cells; upon expression of Prox1, these budding cells adopt a lymphatic vasculature phenotype.</p>
</abstract>
<kwd-group><kwd>lymphangiogenesis/lymphatic endothelial cells/<italic>LYVE-1/Prox1</italic>
/<italic>SLC</italic>
/<italic>VEGFR-3</italic>
</kwd>
</kwd-group>
</article-meta>
</front>
</pmc>
</record>
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