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The nuclear hormone receptor Coup-TFII is required for the initiation and early maintenance of Prox1 expression in lymphatic endothelial cells

Identifieur interne : 002E13 ( Pmc/Corpus ); précédent : 002E12; suivant : 002E14

The nuclear hormone receptor Coup-TFII is required for the initiation and early maintenance of Prox1 expression in lymphatic endothelial cells

Auteurs : R. Sathish Srinivasan ; Xin Geng ; Ying Yang ; Yingdi Wang ; Suraj Mukatira ; Michèle Studer ; Marianna P. R. Porto ; Oleg Lagutin ; Guillermo Oliver

Source :

RBID : PMC:2849126

Abstract

The homeobox gene Prox1 is crucial for mammalian lymphatic vascular development. In the absence of Prox1, lymphatic endothelial cells (LECs) are not specified. The maintenance of LEC identity also requires the constant expression of Prox1. However, the mechanisms controlling the expression of this gene in LECs remain poorly understood. The SRY-related gene Sox18 is required to induce Prox1 expression in venous LEC progenitors. Although Sox18 is also expressed in embryonic arteries, these vessels do not express Prox1, nor do they give rise to LECs. This finding suggests that some venous endothelial cell-specific factor is required for the activation of Prox1. Here we demonstrate that the nuclear hormone receptor Coup-TFII is necessary for the activation of Prox1 in embryonic veins by directly binding a conserved DNA domain in the regulatory region of Prox1. In addition, we show that the direct interaction between nuclear hormone receptors and Prox1 is also necessary for the maintenance of Prox1 expression during early stages of LEC specification and differentiation.


Url:
DOI: 10.1101/gad.1859310
PubMed: 20360386
PubMed Central: 2849126

Links to Exploration step

PMC:2849126

Le document en format XML

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<p>The homeobox gene
<italic>Prox1</italic>
is crucial for mammalian lymphatic vascular development. In the absence of Prox1, lymphatic endothelial cells (LECs) are not specified. The maintenance of LEC identity also requires the constant expression of Prox1. However, the mechanisms controlling the expression of this gene in LECs remain poorly understood. The SRY-related gene
<italic>Sox18</italic>
is required to induce Prox1 expression in venous LEC progenitors. Although
<italic>Sox18</italic>
is also expressed in embryonic arteries, these vessels do not express Prox1, nor do they give rise to LECs. This finding suggests that some venous endothelial cell-specific factor is required for the activation of
<italic>Prox1</italic>
. Here we demonstrate that the nuclear hormone receptor Coup-TFII is necessary for the activation of
<italic>Prox1</italic>
in embryonic veins by directly binding a conserved DNA domain in the regulatory region of
<italic>Prox1</italic>
. In addition, we show that the direct interaction between nuclear hormone receptors and Prox1 is also necessary for the maintenance of
<italic>Prox1</italic>
expression during early stages of LEC specification and differentiation.</p>
</div>
</front>
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<pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front>
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<journal-id journal-id-type="nlm-ta">Genes Dev</journal-id>
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<issn pub-type="ppub">0890-9369</issn>
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<article-id pub-id-type="pmc">2849126</article-id>
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<article-id pub-id-type="doi">10.1101/gad.1859310</article-id>
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<article-title>The nuclear hormone receptor Coup-TFII is required for the initiation and early maintenance of
<italic>Prox1</italic>
expression in lymphatic endothelial cells</article-title>
<alt-title alt-title-type="left-running">Srinivasan et al.</alt-title>
<alt-title alt-title-type="right-running">Coup-TFII regulates
<italic>Prox1</italic>
expression in LECs</alt-title>
</title-group>
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<name>
<surname>Srinivasan</surname>
<given-names>R. Sathish</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Geng</surname>
<given-names>Xin</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Yang</surname>
<given-names>Ying</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Wang</surname>
<given-names>Yingdi</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Mukatira</surname>
<given-names>Suraj</given-names>
</name>
<xref ref-type="aff" rid="aff2">2</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Studer</surname>
<given-names>Michèle</given-names>
</name>
<xref ref-type="aff" rid="aff3">3</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Porto</surname>
<given-names>Marianna P.R.</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Lagutin</surname>
<given-names>Oleg</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Oliver</surname>
<given-names>Guillermo</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
<xref ref-type="corresp" rid="cor1">4</xref>
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<aff id="aff1">
<label>1</label>
Department of Genetics and Tumor Cell Biology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA;</aff>
<aff id="aff2">
<label>2</label>
Hartwell Center for Bioinformatics and Biotechnology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA;</aff>
<aff id="aff3">
<label>3</label>
Developmental Disorders Program, Telethon Institute of Genetics and Medicine, 80131 Napoli, Italy</aff>
<author-notes>
<corresp id="cor1">
<label>4</label>
Corresponding author.E-MAIL
<email>guillermo.oliver@stjude.org</email>
; FAX (901) 595-6035.</corresp>
</author-notes>
<pub-date pub-type="ppub">
<day>1</day>
<month>4</month>
<year>2010</year>
</pub-date>
<volume>24</volume>
<issue>7</issue>
<fpage>696</fpage>
<lpage>707</lpage>
<history>
<date date-type="received">
<day>31</day>
<month>8</month>
<year>2009</year>
</date>
<date date-type="accepted">
<day>18</day>
<month>2</month>
<year>2010</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright © 2010 by Cold Spring Harbor Laboratory Press</copyright-statement>
</permissions>
<self-uri xlink:title="pdf" xlink:type="simple" xlink:href="696.pdf"></self-uri>
<abstract>
<p>The homeobox gene
<italic>Prox1</italic>
is crucial for mammalian lymphatic vascular development. In the absence of Prox1, lymphatic endothelial cells (LECs) are not specified. The maintenance of LEC identity also requires the constant expression of Prox1. However, the mechanisms controlling the expression of this gene in LECs remain poorly understood. The SRY-related gene
<italic>Sox18</italic>
is required to induce Prox1 expression in venous LEC progenitors. Although
<italic>Sox18</italic>
is also expressed in embryonic arteries, these vessels do not express Prox1, nor do they give rise to LECs. This finding suggests that some venous endothelial cell-specific factor is required for the activation of
<italic>Prox1</italic>
. Here we demonstrate that the nuclear hormone receptor Coup-TFII is necessary for the activation of
<italic>Prox1</italic>
in embryonic veins by directly binding a conserved DNA domain in the regulatory region of
<italic>Prox1</italic>
. In addition, we show that the direct interaction between nuclear hormone receptors and Prox1 is also necessary for the maintenance of
<italic>Prox1</italic>
expression during early stages of LEC specification and differentiation.</p>
</abstract>
<kwd-group>
<title>Keywords:</title>
<kwd>Lymphatics</kwd>
<kwd>Prox1</kwd>
<kwd>Coup-TFII</kwd>
<kwd>mouse</kwd>
<kwd>endothelial cell</kwd>
</kwd-group>
</article-meta>
</front>
</pmc>
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