Multiple Mouse Models of Primary Lymphedema Exhibit Distinct Defects in Lymphovenous Valve Development
Identifieur interne : 003358 ( Pmc/Corpus ); précédent : 003357; suivant : 003359Multiple Mouse Models of Primary Lymphedema Exhibit Distinct Defects in Lymphovenous Valve Development
Auteurs : Xin Geng ; Boksik Cha ; Md. Riaj Mahamud ; Kim-Chew Lim ; Robert Silasi-Mansat ; Mohammad K. M. Uddin ; Naoyuki Miura ; Lijun Xia ; Alexander M. Simon ; James Douglas Engel ; Hong Chen ; Florea Lupu ; R. Sathish SrinivasanSource :
- Developmental biology [ 0012-1606 ] ; 2015.
Abstract
Lymph is returned to the blood circulation exclusively via four lymphovenous valves (LVVs). Despite their vital importance, the architecture and development of LVVs is poorly understood. We analyzed the formation of LVVs at the molecular and ultrastructural levels during mouse embryogenesis and identified three critical steps. First, LVV-forming endothelial cells (LVV-ECs) differentiate from PROX1+ progenitors and delaminate from the luminal side of the veins. Second, LVV-ECs aggregate, align perpendicular to the direction of lymph flow and establish lympho-venous connections. Finally, LVVs mature with the recruitment of mural cells. LVV morphogenesis is disrupted in four different mouse models of primary lymphedema and the severity of LVV defects correlate with that of lymphedema. In summary, we have provided the first and the most comprehensive analysis of LVV development. Furthermore, our work suggests that aberrant LVVs contribute to lymphedema.
Url:
DOI: 10.1016/j.ydbio.2015.10.022
PubMed: 26542011
PubMed Central: 4688075
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Multiple Mouse Models of Primary Lymphedema Exhibit Distinct Defects in Lymphovenous Valve Development</title><author><name sortKey="Geng, Xin" sort="Geng, Xin" uniqKey="Geng X" first="Xin" last="Geng">Xin Geng</name><affiliation><nlm:aff id="A1">Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA</nlm:aff></affiliation></author><author><name sortKey="Cha, Boksik" sort="Cha, Boksik" uniqKey="Cha B" first="Boksik" last="Cha">Boksik Cha</name><affiliation><nlm:aff id="A1">Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA</nlm:aff></affiliation></author><author><name sortKey="Mahamud, Md Riaj" sort="Mahamud, Md Riaj" uniqKey="Mahamud M" first="Md. Riaj" last="Mahamud">Md. Riaj Mahamud</name><affiliation><nlm:aff id="A1">Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA</nlm:aff></affiliation></author><author><name sortKey="Lim, Kim Chew" sort="Lim, Kim Chew" uniqKey="Lim K" first="Kim-Chew" last="Lim">Kim-Chew Lim</name><affiliation><nlm:aff id="A3">Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, Michigan, USA</nlm:aff></affiliation></author><author><name sortKey="Silasi Mansat, Robert" sort="Silasi Mansat, Robert" uniqKey="Silasi Mansat R" first="Robert" last="Silasi-Mansat">Robert Silasi-Mansat</name><affiliation><nlm:aff id="A1">Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA</nlm:aff></affiliation></author><author><name sortKey="Uddin, Mohammad K M" sort="Uddin, Mohammad K M" uniqKey="Uddin M" first="Mohammad K. M." last="Uddin">Mohammad K. M. Uddin</name><affiliation><nlm:aff id="A4">Department of Biochemistry, Hamamatsu University School of Medicine, Hamamatsu, Japan</nlm:aff></affiliation></author><author><name sortKey="Miura, Naoyuki" sort="Miura, Naoyuki" uniqKey="Miura N" first="Naoyuki" last="Miura">Naoyuki Miura</name><affiliation><nlm:aff id="A4">Department of Biochemistry, Hamamatsu University School of Medicine, Hamamatsu, Japan</nlm:aff></affiliation></author><author><name sortKey="Xia, Lijun" sort="Xia, Lijun" uniqKey="Xia L" first="Lijun" last="Xia">Lijun Xia</name><affiliation><nlm:aff id="A1">Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA</nlm:aff></affiliation></author><author><name sortKey="Simon, Alexander M" sort="Simon, Alexander M" uniqKey="Simon A" first="Alexander M." last="Simon">Alexander M. Simon</name><affiliation><nlm:aff id="A5">Department of Physiology, University of Arizona, Tucson, Arizona, USA</nlm:aff></affiliation></author><author><name sortKey="Engel, James Douglas" sort="Engel, James Douglas" uniqKey="Engel J" first="James Douglas" last="Engel">James Douglas Engel</name><affiliation><nlm:aff id="A3">Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, Michigan, USA</nlm:aff></affiliation></author><author><name sortKey="Chen, Hong" sort="Chen, Hong" uniqKey="Chen H" first="Hong" last="Chen">Hong Chen</name><affiliation><nlm:aff id="A1">Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA</nlm:aff></affiliation></author><author><name sortKey="Lupu, Florea" sort="Lupu, Florea" uniqKey="Lupu F" first="Florea" last="Lupu">Florea Lupu</name><affiliation><nlm:aff id="A1">Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA</nlm:aff></affiliation></author><author><name sortKey="Srinivasan, R Sathish" sort="Srinivasan, R Sathish" uniqKey="Srinivasan R" first="R. Sathish" last="Srinivasan">R. Sathish Srinivasan</name><affiliation><nlm:aff id="A1">Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">26542011</idno><idno type="pmc">4688075</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4688075</idno><idno type="RBID">PMC:4688075</idno><idno type="doi">10.1016/j.ydbio.2015.10.022</idno><date when="2015">2015</date><idno type="wicri:Area/Pmc/Corpus">003358</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">003358</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Multiple Mouse Models of Primary Lymphedema Exhibit Distinct Defects in Lymphovenous Valve Development</title><author><name sortKey="Geng, Xin" sort="Geng, Xin" uniqKey="Geng X" first="Xin" last="Geng">Xin Geng</name><affiliation><nlm:aff id="A1">Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA</nlm:aff></affiliation></author><author><name sortKey="Cha, Boksik" sort="Cha, Boksik" uniqKey="Cha B" first="Boksik" last="Cha">Boksik Cha</name><affiliation><nlm:aff id="A1">Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA</nlm:aff></affiliation></author><author><name sortKey="Mahamud, Md Riaj" sort="Mahamud, Md Riaj" uniqKey="Mahamud M" first="Md. Riaj" last="Mahamud">Md. Riaj Mahamud</name><affiliation><nlm:aff id="A1">Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA</nlm:aff></affiliation></author><author><name sortKey="Lim, Kim Chew" sort="Lim, Kim Chew" uniqKey="Lim K" first="Kim-Chew" last="Lim">Kim-Chew Lim</name><affiliation><nlm:aff id="A3">Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, Michigan, USA</nlm:aff></affiliation></author><author><name sortKey="Silasi Mansat, Robert" sort="Silasi Mansat, Robert" uniqKey="Silasi Mansat R" first="Robert" last="Silasi-Mansat">Robert Silasi-Mansat</name><affiliation><nlm:aff id="A1">Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA</nlm:aff></affiliation></author><author><name sortKey="Uddin, Mohammad K M" sort="Uddin, Mohammad K M" uniqKey="Uddin M" first="Mohammad K. M." last="Uddin">Mohammad K. M. Uddin</name><affiliation><nlm:aff id="A4">Department of Biochemistry, Hamamatsu University School of Medicine, Hamamatsu, Japan</nlm:aff></affiliation></author><author><name sortKey="Miura, Naoyuki" sort="Miura, Naoyuki" uniqKey="Miura N" first="Naoyuki" last="Miura">Naoyuki Miura</name><affiliation><nlm:aff id="A4">Department of Biochemistry, Hamamatsu University School of Medicine, Hamamatsu, Japan</nlm:aff></affiliation></author><author><name sortKey="Xia, Lijun" sort="Xia, Lijun" uniqKey="Xia L" first="Lijun" last="Xia">Lijun Xia</name><affiliation><nlm:aff id="A1">Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA</nlm:aff></affiliation></author><author><name sortKey="Simon, Alexander M" sort="Simon, Alexander M" uniqKey="Simon A" first="Alexander M." last="Simon">Alexander M. Simon</name><affiliation><nlm:aff id="A5">Department of Physiology, University of Arizona, Tucson, Arizona, USA</nlm:aff></affiliation></author><author><name sortKey="Engel, James Douglas" sort="Engel, James Douglas" uniqKey="Engel J" first="James Douglas" last="Engel">James Douglas Engel</name><affiliation><nlm:aff id="A3">Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, Michigan, USA</nlm:aff></affiliation></author><author><name sortKey="Chen, Hong" sort="Chen, Hong" uniqKey="Chen H" first="Hong" last="Chen">Hong Chen</name><affiliation><nlm:aff id="A1">Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA</nlm:aff></affiliation></author><author><name sortKey="Lupu, Florea" sort="Lupu, Florea" uniqKey="Lupu F" first="Florea" last="Lupu">Florea Lupu</name><affiliation><nlm:aff id="A1">Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA</nlm:aff></affiliation></author><author><name sortKey="Srinivasan, R Sathish" sort="Srinivasan, R Sathish" uniqKey="Srinivasan R" first="R. Sathish" last="Srinivasan">R. Sathish Srinivasan</name><affiliation><nlm:aff id="A1">Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA</nlm:aff></affiliation></author></analytic><series><title level="j">Developmental biology</title><idno type="ISSN">0012-1606</idno><idno type="eISSN">1095-564X</idno><imprint><date when="2015">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="P1">Lymph is returned to the blood circulation exclusively via four lymphovenous valves (LVVs). Despite their vital importance, the architecture and development of LVVs is poorly understood. We analyzed the formation of LVVs at the molecular and ultrastructural levels during mouse embryogenesis and identified three critical steps. First, LVV-forming endothelial cells (LVV-ECs) differentiate from PROX1<sup>+</sup> progenitors and delaminate from the luminal side of the veins. Second, LVV-ECs aggregate, align perpendicular to the direction of lymph flow and establish lympho-venous connections. Finally, LVVs mature with the recruitment of mural cells. LVV morphogenesis is disrupted in four different mouse models of primary lymphedema and the severity of LVV defects correlate with that of lymphedema. In summary, we have provided the first and the most comprehensive analysis of LVV development. Furthermore, our work suggests that aberrant LVVs contribute to lymphedema.</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>
<pmc-dir>properties manuscript</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-journal-id">0372762</journal-id><journal-id journal-id-type="pubmed-jr-id">3389</journal-id><journal-id journal-id-type="nlm-ta">Dev Biol</journal-id><journal-id journal-id-type="iso-abbrev">Dev. Biol.</journal-id><journal-title-group><journal-title>Developmental biology</journal-title></journal-title-group><issn pub-type="ppub">0012-1606</issn><issn pub-type="epub">1095-564X</issn></journal-meta><article-meta><article-id pub-id-type="pmid">26542011</article-id><article-id pub-id-type="pmc">4688075</article-id><article-id pub-id-type="doi">10.1016/j.ydbio.2015.10.022</article-id><article-id pub-id-type="manuscript">NIHMS736429</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Multiple Mouse Models of Primary Lymphedema Exhibit Distinct Defects in Lymphovenous Valve Development</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Geng</surname><given-names>Xin</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Cha</surname><given-names>Boksik</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Mahamud</surname><given-names>Md. Riaj</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Lim</surname><given-names>Kim-Chew</given-names></name><xref ref-type="aff" rid="A3">3</xref></contrib><contrib contrib-type="author"><name><surname>Silasi-Mansat</surname><given-names>Robert</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Uddin</surname><given-names>Mohammad K.M.</given-names></name><xref ref-type="aff" rid="A4">4</xref></contrib><contrib contrib-type="author"><name><surname>Miura</surname><given-names>Naoyuki</given-names></name><xref ref-type="aff" rid="A4">4</xref></contrib><contrib contrib-type="author"><name><surname>Xia</surname><given-names>Lijun</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Simon</surname><given-names>Alexander M.</given-names></name><xref ref-type="aff" rid="A5">5</xref></contrib><contrib contrib-type="author"><name><surname>Engel</surname><given-names>James Douglas</given-names></name><xref ref-type="aff" rid="A3">3</xref></contrib><contrib contrib-type="author"><name><surname>Chen</surname><given-names>Hong</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Lupu</surname><given-names>Florea</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Srinivasan</surname><given-names>R. Sathish</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A2">2</xref><xref ref-type="corresp" rid="cor1">*</xref></contrib></contrib-group><aff id="A1"><label>1</label>Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA</aff><aff id="A2"><label>2</label>Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA</aff><aff id="A3"><label>3</label>Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, Michigan, USA</aff><aff id="A4"><label>4</label>Department of Biochemistry, Hamamatsu University School of Medicine, Hamamatsu, Japan</aff><aff id="A5"><label>5</label>Department of Physiology, University of Arizona, Tucson, Arizona, USA</aff><author-notes><corresp id="cor1"><label>*</label>Correspondence: <email>sathish-srinivasan@omrf.org</email></corresp></author-notes><pub-date pub-type="nihms-submitted"><day>28</day><month>11</month><year>2015</year></pub-date><pub-date pub-type="epub"><day>02</day><month>11</month><year>2015</year></pub-date><pub-date pub-type="ppub"><day>1</day><month>1</month><year>2016</year></pub-date><pub-date pub-type="pmc-release"><day>01</day><month>1</month><year>2017</year></pub-date><volume>409</volume><issue>1</issue><fpage>218</fpage><lpage>233</lpage><pmc-comment>elocation-id from pubmed: 10.1016/j.ydbio.2015.10.022</pmc-comment>
<abstract><p id="P1">Lymph is returned to the blood circulation exclusively via four lymphovenous valves (LVVs). Despite their vital importance, the architecture and development of LVVs is poorly understood. We analyzed the formation of LVVs at the molecular and ultrastructural levels during mouse embryogenesis and identified three critical steps. First, LVV-forming endothelial cells (LVV-ECs) differentiate from PROX1<sup>+</sup> progenitors and delaminate from the luminal side of the veins. Second, LVV-ECs aggregate, align perpendicular to the direction of lymph flow and establish lympho-venous connections. Finally, LVVs mature with the recruitment of mural cells. LVV morphogenesis is disrupted in four different mouse models of primary lymphedema and the severity of LVV defects correlate with that of lymphedema. In summary, we have provided the first and the most comprehensive analysis of LVV development. Furthermore, our work suggests that aberrant LVVs contribute to lymphedema.</p></abstract></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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