The Prox1–Vegfr3 feedback loop maintains the identity and the number of lymphatic endothelial cell progenitors
Identifieur interne : 006B57 ( Ncbi/Merge ); précédent : 006B56; suivant : 006B58The Prox1–Vegfr3 feedback loop maintains the identity and the number of lymphatic endothelial cell progenitors
Auteurs : R. Sathish Srinivasan ; Noelia Escobedo ; Ying Yang ; Ashley Interiano ; Miriam E. Dillard ; David Finkelstein [États-Unis] ; Suraj Mukatira [États-Unis] ; Hyea Jin Gil ; Harri Nurmi [Finlande] ; Kari Alitalo [Finlande] ; Guillermo OliverSource :
- Genes & Development [ 0890-9369 ] ; 2014.
Abstract
The lack of Prox1 activity results in the complete absence of lymphatic endothelial cells (LECs). Here, Srinivasan et al. identified Vegfr3, the cognate receptor of the lymphangiogenic growth factor Vegfc, as a dosage-dependent, direct in vivo target of Prox1. Vegfr3 regulates Prox1 by establishing a feedback loop necessary to maintain the identity of LEC progenitors, and Vegfc-mediated activation of Vegfr3 signaling is necessary to maintain Prox1 expression in LEC progenitors.
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DOI: 10.1101/gad.216226.113
PubMed: 25274728
PubMed Central: 4180978
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Sathish Srinivasan</name><affiliation><nlm:aff id="aff1">Department of Genetics,</nlm:aff></affiliation></author><author><name sortKey="Escobedo, Noelia" sort="Escobedo, Noelia" uniqKey="Escobedo N" first="Noelia" last="Escobedo">Noelia Escobedo</name><affiliation><nlm:aff id="aff1">Department of Genetics,</nlm:aff></affiliation></author><author><name sortKey="Yang, Ying" sort="Yang, Ying" uniqKey="Yang Y" first="Ying" last="Yang">Ying Yang</name><affiliation><nlm:aff id="aff1">Department of Genetics,</nlm:aff></affiliation></author><author><name sortKey="Interiano, Ashley" sort="Interiano, Ashley" uniqKey="Interiano A" first="Ashley" last="Interiano">Ashley Interiano</name><affiliation><nlm:aff id="aff1">Department of Genetics,</nlm:aff></affiliation></author><author><name sortKey="Dillard, Miriam E" sort="Dillard, Miriam E" uniqKey="Dillard M" first="Miriam E." last="Dillard">Miriam E. 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Sathish" last="Srinivasan">R. Sathish Srinivasan</name><affiliation><nlm:aff id="aff1">Department of Genetics,</nlm:aff></affiliation></author><author><name sortKey="Escobedo, Noelia" sort="Escobedo, Noelia" uniqKey="Escobedo N" first="Noelia" last="Escobedo">Noelia Escobedo</name><affiliation><nlm:aff id="aff1">Department of Genetics,</nlm:aff></affiliation></author><author><name sortKey="Yang, Ying" sort="Yang, Ying" uniqKey="Yang Y" first="Ying" last="Yang">Ying Yang</name><affiliation><nlm:aff id="aff1">Department of Genetics,</nlm:aff></affiliation></author><author><name sortKey="Interiano, Ashley" sort="Interiano, Ashley" uniqKey="Interiano A" first="Ashley" last="Interiano">Ashley Interiano</name><affiliation><nlm:aff id="aff1">Department of Genetics,</nlm:aff></affiliation></author><author><name sortKey="Dillard, Miriam E" sort="Dillard, Miriam E" uniqKey="Dillard M" first="Miriam E." last="Dillard">Miriam E. Dillard</name><affiliation><nlm:aff id="aff1">Department of Genetics,</nlm:aff></affiliation></author><author><name sortKey="Finkelstein, David" sort="Finkelstein, David" uniqKey="Finkelstein D" first="David" last="Finkelstein">David Finkelstein</name><affiliation wicri:level="1"><nlm:aff id="aff2">Department of Computational Biology, St. Jude Children’s Research Hospital, Memphis, Tennessee 38105, USA;</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Computational Biology, St. Jude Children’s Research Hospital, Memphis, Tennessee 38105</wicri:regionArea><wicri:noRegion>Tennessee 38105</wicri:noRegion></affiliation></author><author><name sortKey="Mukatira, Suraj" sort="Mukatira, Suraj" uniqKey="Mukatira S" first="Suraj" last="Mukatira">Suraj Mukatira</name><affiliation wicri:level="1"><nlm:aff id="aff2">Department of Computational Biology, St. Jude Children’s Research Hospital, Memphis, Tennessee 38105, USA;</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Computational Biology, St. Jude Children’s Research Hospital, Memphis, Tennessee 38105</wicri:regionArea><wicri:noRegion>Tennessee 38105</wicri:noRegion></affiliation></author><author><name sortKey="Gil, Hyea Jin" sort="Gil, Hyea Jin" uniqKey="Gil H" first="Hyea Jin" last="Gil">Hyea Jin Gil</name><affiliation><nlm:aff id="aff1">Department of Genetics,</nlm:aff></affiliation></author><author><name sortKey="Nurmi, Harri" sort="Nurmi, Harri" uniqKey="Nurmi H" first="Harri" last="Nurmi">Harri Nurmi</name><affiliation><nlm:aff id="aff3">Wihuri Research Institute,</nlm:aff></affiliation><affiliation wicri:level="4"><nlm:aff id="aff4">Translational Cancer Biology Program, University of Helsinki, Helsinki 00014, Finland</nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Translational Cancer Biology Program, University of Helsinki, Helsinki 00014</wicri:regionArea><orgName type="university">Université d'Helsinki</orgName><placeName><settlement type="city">Helsinki</settlement><region type="région" nuts="2">Uusimaa</region></placeName></affiliation></author><author><name sortKey="Alitalo, Kari" sort="Alitalo, Kari" uniqKey="Alitalo K" first="Kari" last="Alitalo">Kari Alitalo</name><affiliation><nlm:aff id="aff3">Wihuri Research Institute,</nlm:aff><country>Finlande</country><placeName><settlement type="city">Helsinki</settlement><region type="région" nuts="2">Uusimaa</region></placeName><orgName type="university">Université d'Helsinki</orgName></affiliation><affiliation wicri:level="4"><nlm:aff id="aff4">Translational Cancer Biology Program, University of Helsinki, Helsinki 00014, Finland</nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Translational Cancer Biology Program, University of Helsinki, Helsinki 00014</wicri:regionArea><orgName type="university">Université d'Helsinki</orgName><placeName><settlement type="city">Helsinki</settlement><region type="région" nuts="2">Uusimaa</region></placeName><placeName><settlement type="city">Helsinki</settlement><region type="région" nuts="2">Uusimaa</region></placeName><orgName type="university">Université d'Helsinki</orgName></affiliation></author><author><name sortKey="Oliver, Guillermo" sort="Oliver, Guillermo" uniqKey="Oliver G" first="Guillermo" last="Oliver">Guillermo Oliver</name><affiliation><nlm:aff id="aff1">Department of Genetics,</nlm:aff></affiliation></author></analytic><series><title level="j">Genes & Development</title><idno type="ISSN">0890-9369</idno><idno type="eISSN">1549-5477</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>The lack of Prox1 activity results in the complete absence of lymphatic endothelial cells (LECs). Here, Srinivasan et al. identified Vegfr3, the cognate receptor of the lymphangiogenic growth factor Vegfc, as a dosage-dependent, direct in vivo target of Prox1. Vegfr3 regulates Prox1 by establishing a feedback loop necessary to maintain the identity of LEC progenitors, and Vegfc-mediated activation of Vegfr3 signaling is necessary to maintain Prox1 expression in LEC progenitors.</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">Genes Dev</journal-id><journal-id journal-id-type="iso-abbrev">Genes Dev</journal-id><journal-id journal-id-type="hwp">genesdev</journal-id><journal-id journal-id-type="pmc">genesdev</journal-id><journal-id journal-id-type="publisher-id">GAD</journal-id><journal-title-group><journal-title>Genes & Development</journal-title></journal-title-group><issn pub-type="ppub">0890-9369</issn><issn pub-type="epub">1549-5477</issn><publisher><publisher-name>Cold Spring Harbor Laboratory Press</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">25274728</article-id><article-id pub-id-type="pmc">4180978</article-id><article-id pub-id-type="medline">8711660</article-id><article-id pub-id-type="doi">10.1101/gad.216226.113</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Paper</subject></subj-group></article-categories><title-group><article-title>The Prox1–Vegfr3 feedback loop maintains the identity and the number of lymphatic endothelial cell progenitors</article-title><alt-title alt-title-type="left-running">Srinivasan et al.</alt-title><alt-title alt-title-type="right-running">Regulation of lymphatic progenitor identity</alt-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Srinivasan</surname><given-names>R. Sathish</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><xref ref-type="author-notes" rid="fn1"><sup>5</sup></xref><xref ref-type="author-notes" rid="fn3"><sup>7</sup></xref></contrib><contrib contrib-type="author"><name><surname>Escobedo</surname><given-names>Noelia</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><xref ref-type="author-notes" rid="fn3"><sup>7</sup></xref></contrib><contrib contrib-type="author"><name><surname>Yang</surname><given-names>Ying</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><xref ref-type="author-notes" rid="fn2"><sup>6</sup></xref><xref ref-type="author-notes" rid="fn3"><sup>7</sup></xref></contrib><contrib contrib-type="author"><name><surname>Interiano</surname><given-names>Ashley</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Dillard</surname><given-names>Miriam E.</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Finkelstein</surname><given-names>David</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Mukatira</surname><given-names>Suraj</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Gil</surname><given-names>Hyea Jin</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Nurmi</surname><given-names>Harri</given-names></name><xref ref-type="aff" rid="aff3"><sup>3</sup></xref><xref ref-type="aff" rid="aff4"><sup>4</sup></xref></contrib><contrib contrib-type="author"><name><surname>Alitalo</surname><given-names>Kari</given-names></name><xref ref-type="aff" rid="aff3"><sup>3</sup></xref><xref ref-type="aff" rid="aff4"><sup>4</sup></xref></contrib><contrib contrib-type="author" corresp="yes"><name><surname>Oliver</surname><given-names>Guillermo</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><aff id="aff1"><label>1</label>Department of Genetics,</aff><aff id="aff2"><label>2</label>Department of Computational Biology, St. Jude Children’s Research Hospital, Memphis, Tennessee 38105, USA;</aff><aff id="aff3"><label>3</label>Wihuri Research Institute,</aff><aff id="aff4"><label>4</label>Translational Cancer Biology Program, University of Helsinki, Helsinki 00014, Finland</aff></contrib-group><author-notes><fn fn-type="present-address" id="fn1"><p>Present addresses: <sup>5</sup>Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, 73104 USA;</p></fn><fn fn-type="present-address" id="fn2"><label>6</label><p>Division of Animal Sciences, Bond Life Sciences Center, University of Missouri, Columbia, MO 65211, USA.</p></fn><fn fn-type="equal" id="fn3"><label>7</label><p>These authors contributed equally to this work.</p></fn><corresp id="cor1">Corresponding author: <email>guillermo.oliver@stjude.org</email></corresp></author-notes><pub-date pub-type="ppub"><day>1</day><month>10</month><year>2014</year></pub-date><volume>28</volume><issue>19</issue><fpage>2175</fpage><lpage>2187</lpage><history><date date-type="received"><day>18</day><month>2</month><year>2013</year></date><date date-type="accepted"><day>21</day><month>8</month><year>2014</year></date></history><permissions><copyright-statement><ext-link ext-link-type="uri" xlink:href="http://genesdev.cshlp.org/site/misc/terms.xhtml">© 2014 Srinivasan et al.; Published by Cold Spring Harbor Laboratory Press</ext-link></copyright-statement><copyright-year>2014</copyright-year><license license-type="creative-commons" xlink:href="http://creativecommons.org/licenses/by-nc/4.0/"><license-p>This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see <ext-link ext-link-type="uri" xlink:href="http://genesdev.cshlp.org/site/misc/terms.xhtml">http://genesdev.cshlp.org/site/misc/terms.xhtml</ext-link>). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by-nc/4.0/">http://creativecommons.org/licenses/by-nc/4.0/</ext-link>.</license-p></license></permissions><self-uri xlink:title="pdf" xlink:href="2175.pdf"></self-uri><abstract abstract-type="precis"><p>The lack of Prox1 activity results in the complete absence of lymphatic endothelial cells (LECs). Here, Srinivasan et al. identified Vegfr3, the cognate receptor of the lymphangiogenic growth factor Vegfc, as a dosage-dependent, direct in vivo target of Prox1. Vegfr3 regulates Prox1 by establishing a feedback loop necessary to maintain the identity of LEC progenitors, and Vegfc-mediated activation of Vegfr3 signaling is necessary to maintain Prox1 expression in LEC progenitors.</p></abstract><abstract><p>The mammalian lymphatic vasculature is important for returning fluids from the extracellular tissue milieu back to the blood circulation. We showed previously that Prox1 dosage is important for the development of the mammalian lymphatic vasculature. The lack of Prox1 activity results in the complete absence of lymphatic endothelial cells (LECs). In <italic>Prox1</italic> heterozygous embryos, the number of LECs is reduced because of a decrease in the progenitor pool in the cardinal vein. This reduction is caused by some progenitor cells being unable to maintain <italic>Prox1</italic> expression. In this study, we identified <italic>Vegfr3</italic>, the cognate receptor of the lymphangiogenic growth factor <italic>Vegfc</italic>, as a dosage-dependent, direct in vivo target of Prox1. Using various mouse models, we also determined that Vegfr3 regulates <italic>Prox1</italic> by establishing a feedback loop necessary to maintain the identity of LEC progenitors and that Vegfc-mediated activation of <italic>Vegfr3</italic> signaling is necessary to maintain <italic>Prox1</italic> expression in LEC progenitors. We propose that this feedback loop is the main sensing mechanism controlling the number of LEC progenitors and, as a consequence, the number of budding LECs that will form the embryonic lymphatic vasculature.</p></abstract><kwd-group><kwd>Prox1</kwd><kwd>Vegfr3</kwd><kwd>lymphatics</kwd><kwd>endothelial cell</kwd><kwd>progenitor</kwd><kwd>mouse</kwd></kwd-group><counts><page-count count="13"></page-count></counts></article-meta></front></pmc><affiliations><list><country><li>Finlande</li><li>États-Unis</li></country><region><li>Uusimaa</li></region><settlement><li>Helsinki</li></settlement><orgName><li>Université d'Helsinki</li></orgName></list><tree><noCountry><name sortKey="Dillard, Miriam E" sort="Dillard, Miriam E" uniqKey="Dillard M" first="Miriam E." last="Dillard">Miriam E. Dillard</name><name sortKey="Escobedo, Noelia" sort="Escobedo, Noelia" uniqKey="Escobedo N" first="Noelia" last="Escobedo">Noelia Escobedo</name><name sortKey="Gil, Hyea Jin" sort="Gil, Hyea Jin" uniqKey="Gil H" first="Hyea Jin" last="Gil">Hyea Jin Gil</name><name sortKey="Interiano, Ashley" sort="Interiano, Ashley" uniqKey="Interiano A" first="Ashley" last="Interiano">Ashley Interiano</name><name sortKey="Oliver, Guillermo" sort="Oliver, Guillermo" uniqKey="Oliver G" first="Guillermo" last="Oliver">Guillermo Oliver</name><name sortKey="Srinivasan, R Sathish" sort="Srinivasan, R Sathish" uniqKey="Srinivasan R" first="R. Sathish" last="Srinivasan">R. Sathish Srinivasan</name><name sortKey="Yang, Ying" sort="Yang, Ying" uniqKey="Yang Y" first="Ying" last="Yang">Ying Yang</name></noCountry><country name="États-Unis"><noRegion><name sortKey="Finkelstein, David" sort="Finkelstein, David" uniqKey="Finkelstein D" first="David" last="Finkelstein">David Finkelstein</name></noRegion><name sortKey="Mukatira, Suraj" sort="Mukatira, Suraj" uniqKey="Mukatira S" first="Suraj" last="Mukatira">Suraj Mukatira</name></country><country name="Finlande"><region name="Uusimaa"><name sortKey="Nurmi, Harri" sort="Nurmi, Harri" uniqKey="Nurmi H" first="Harri" last="Nurmi">Harri Nurmi</name></region><name sortKey="Alitalo, Kari" sort="Alitalo, Kari" uniqKey="Alitalo K" first="Kari" last="Alitalo">Kari Alitalo</name><name sortKey="Alitalo, Kari" sort="Alitalo, Kari" uniqKey="Alitalo K" first="Kari" last="Alitalo">Kari Alitalo</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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