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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Abnormal embryonic lymphatic vessel development in <italic>Tie1</italic> hypomorphic mice</title><author><name sortKey="Qu, Xianghu" sort="Qu, Xianghu" uniqKey="Qu X" first="Xianghu" last="Qu">Xianghu Qu</name><affiliation><nlm:aff id="A1"> Division of Pediatric Cardiology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.</nlm:aff></affiliation></author><author><name sortKey="Tompkins, Kevin" sort="Tompkins, Kevin" uniqKey="Tompkins K" first="Kevin" last="Tompkins">Kevin Tompkins</name><affiliation><nlm:aff id="A1"> Division of Pediatric Cardiology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.</nlm:aff></affiliation></author><author><name sortKey="Batts, Lorene E" sort="Batts, Lorene E" uniqKey="Batts L" first="Lorene E." last="Batts">Lorene E. Batts</name><affiliation><nlm:aff id="A1"> Division of Pediatric Cardiology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.</nlm:aff></affiliation></author><author><name sortKey="Puri, Mira" sort="Puri, Mira" uniqKey="Puri M" first="Mira" last="Puri">Mira Puri</name><affiliation><nlm:aff id="A2"> Sunnybrook and Women’s College Health Sciences Center, University of Toronto, Toronto, Ontario M4N 3M5, Canada.</nlm:aff></affiliation></author><author><name sortKey="Baldwin, Scott" sort="Baldwin, Scott" uniqKey="Baldwin S" first="Scott" last="Baldwin">Scott Baldwin</name><affiliation><nlm:aff id="A1"> Division of Pediatric Cardiology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A3"> Department of Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">20223757</idno><idno type="pmc">2847464</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2847464</idno><idno type="RBID">PMC:2847464</idno><idno type="doi">10.1242/dev.043380</idno><date when="2010">2010</date><idno type="wicri:Area/Pmc/Corpus">002D82</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">002D82</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Abnormal embryonic lymphatic vessel development in <italic>Tie1</italic> hypomorphic mice</title><author><name sortKey="Qu, Xianghu" sort="Qu, Xianghu" uniqKey="Qu X" first="Xianghu" last="Qu">Xianghu Qu</name><affiliation><nlm:aff id="A1"> Division of Pediatric Cardiology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.</nlm:aff></affiliation></author><author><name sortKey="Tompkins, Kevin" sort="Tompkins, Kevin" uniqKey="Tompkins K" first="Kevin" last="Tompkins">Kevin Tompkins</name><affiliation><nlm:aff id="A1"> Division of Pediatric Cardiology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.</nlm:aff></affiliation></author><author><name sortKey="Batts, Lorene E" sort="Batts, Lorene E" uniqKey="Batts L" first="Lorene E." last="Batts">Lorene E. Batts</name><affiliation><nlm:aff id="A1"> Division of Pediatric Cardiology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.</nlm:aff></affiliation></author><author><name sortKey="Puri, Mira" sort="Puri, Mira" uniqKey="Puri M" first="Mira" last="Puri">Mira Puri</name><affiliation><nlm:aff id="A2"> Sunnybrook and Women’s College Health Sciences Center, University of Toronto, Toronto, Ontario M4N 3M5, Canada.</nlm:aff></affiliation></author><author><name sortKey="Baldwin, Scott" sort="Baldwin, Scott" uniqKey="Baldwin S" first="Scott" last="Baldwin">Scott Baldwin</name><affiliation><nlm:aff id="A1"> Division of Pediatric Cardiology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A3"> Department of Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.</nlm:aff></affiliation></author></analytic><series><title level="j">Development (Cambridge, England)</title><idno type="ISSN">0950-1991</idno><idno type="eISSN">1477-9129</idno><imprint><date when="2010">2010</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="P1">Tie1 is an endothelial receptor tyrosine kinase that is essential for development and maintenance of the vascular system; however, the role of Tie1 in development of the lymphatic vasculature is unknown. To address this question, we first documented that Tie1 is expressed at the earliest stages of lymphangiogenesis in Prox1-positive venous lymphatic endothelial cell (LEC) progenitors. LEC Tie1 expression is maintained throughout embryonic development and persists in postnatal mice. We then generated two lines of <italic>Tie1</italic> mutant mice: a hypomorphic allele, which has reduced expression of Tie1, and a conditional allele. Reduction of Tie1 levels resulted in abnormal lymphatic patterning and in dilated and disorganized lymphatic vessels in all tissues examined and in impaired lymphatic drainage in embryonic skin. Homozygous hypomorphic mice also exhibited abnormally dilated jugular lymphatic vessels due to increased production of Prox1-positive LECs during initial lymphangiogenesis, indicating that Tie1 is required for the early stages of normal lymphangiogenesis. During later stages of lymphatic development, we observed an increase in LEC apoptosis in the hypomorphic embryos after mid-gestation that was associated with abnormal regression of the lymphatic vasculature. Therefore, Tie1 is required for early LEC proliferation and subsequent survival of developing LECs. The severity of the phenotypes observed correlated with the expression levels of Tie1, confirming a dosage dependence for Tie1 in LEC integrity and survival. No defects were observed in the arterial or venous vasculature. These results suggest that the developing lymphatic vasculature is particularly sensitive to alterations in Tie1 expression.</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">Development</journal-id><journal-id journal-id-type="hwp">develop</journal-id><journal-id journal-id-type="publisher-id">dev</journal-id><journal-title-group><journal-title>Development (Cambridge, England)</journal-title></journal-title-group><issn pub-type="ppub">0950-1991</issn><issn pub-type="epub">1477-9129</issn><publisher><publisher-name>Company of Biologists</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">20223757</article-id><article-id pub-id-type="pmc">2847464</article-id><article-id pub-id-type="doi">10.1242/dev.043380</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Articles</subject></subj-group></article-categories><title-group><article-title>Abnormal embryonic lymphatic vessel development in <italic>Tie1</italic> hypomorphic mice</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Qu</surname><given-names>Xianghu</given-names></name><xref ref-type="aff" rid="A1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Tompkins</surname><given-names>Kevin</given-names></name><xref ref-type="aff" rid="A1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Batts</surname><given-names>Lorene E.</given-names></name><xref ref-type="aff" rid="A1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Puri</surname><given-names>Mira</given-names></name><xref ref-type="aff" rid="A2"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Baldwin</surname><given-names>Scott</given-names></name><xref ref-type="aff" rid="A1"><sup>1</sup></xref><xref ref-type="aff" rid="A3"><sup>3</sup></xref><xref ref-type="corresp" rid="cor1"><sup>*</sup></xref></contrib><aff id="A1"><label>1</label> Division of Pediatric Cardiology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.</aff><aff id="A2"><label>2</label> Sunnybrook and Women’s College Health Sciences Center, University of Toronto, Toronto, Ontario M4N 3M5, Canada.</aff><aff id="A3"><label>3</label> Department of Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.</aff></contrib-group><author-notes><corresp id="cor1"><label>*</label> Author for correspondence (<email>scott.baldwin@vanderbilt.edu</email>)</corresp></author-notes><pub-date pub-type="ppub"><day>15</day><month>4</month><year>2010</year></pub-date><pub-date pub-type="pmc-release"><day>15</day><month>4</month><year>2011</year></pub-date><pmc-comment> PMC Release delay is 12 months and 0 days and was based on the
<volume>137</volume><issue>8</issue><fpage>1285</fpage><lpage>1295</lpage><history><date date-type="accepted"><day>5</day><month>2</month><year>2010</year></date></history><permissions><copyright-statement>© 2010.</copyright-statement></permissions><self-uri xlink:title="pdf" xlink:type="simple" xlink:href="1285.pdf"></self-uri><abstract><p id="P1">Tie1 is an endothelial receptor tyrosine kinase that is essential for development and maintenance of the vascular system; however, the role of Tie1 in development of the lymphatic vasculature is unknown. To address this question, we first documented that Tie1 is expressed at the earliest stages of lymphangiogenesis in Prox1-positive venous lymphatic endothelial cell (LEC) progenitors. LEC Tie1 expression is maintained throughout embryonic development and persists in postnatal mice. We then generated two lines of <italic>Tie1</italic> mutant mice: a hypomorphic allele, which has reduced expression of Tie1, and a conditional allele. Reduction of Tie1 levels resulted in abnormal lymphatic patterning and in dilated and disorganized lymphatic vessels in all tissues examined and in impaired lymphatic drainage in embryonic skin. Homozygous hypomorphic mice also exhibited abnormally dilated jugular lymphatic vessels due to increased production of Prox1-positive LECs during initial lymphangiogenesis, indicating that Tie1 is required for the early stages of normal lymphangiogenesis. During later stages of lymphatic development, we observed an increase in LEC apoptosis in the hypomorphic embryos after mid-gestation that was associated with abnormal regression of the lymphatic vasculature. Therefore, Tie1 is required for early LEC proliferation and subsequent survival of developing LECs. The severity of the phenotypes observed correlated with the expression levels of Tie1, confirming a dosage dependence for Tie1 in LEC integrity and survival. No defects were observed in the arterial or venous vasculature. These results suggest that the developing lymphatic vasculature is particularly sensitive to alterations in Tie1 expression.</p></abstract><kwd-group><kwd><italic>Tie1</italic></kwd><kwd>Lymphatic development</kwd><kwd>Hypomorphic</kwd><kwd>Proliferation</kwd><kwd>Apoptosis</kwd><kwd>Mouse</kwd></kwd-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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