Integrin-α9 is required for fibronectin matrix assembly during lymphatic valve morphogenesis
Identifieur interne : 006232 ( Main/Exploration ); précédent : 006231; suivant : 006233Integrin-α9 is required for fibronectin matrix assembly during lymphatic valve morphogenesis
Auteurs : Eleni Bazigou [Royaume-Uni] ; Sherry Xie [Royaume-Uni] ; Chun Chen [États-Unis] ; Anne Weston [Royaume-Uni] ; Naoyuki Miura [Japon] ; Lydia Sorokin [Allemagne] ; Ralf Adams [Royaume-Uni, Allemagne] ; Andrés F. Muro [Italie] ; Dean Sheppard [États-Unis] ; Taija Makinen [Royaume-Uni]Source :
- Developmental cell [ 1534-5807 ] ; 2009.
Descripteurs français
- KwdFr :
- Animaux, Antigènes CD31 (métabolisme), Cellules endothéliales (cytologie), Cellules endothéliales (métabolisme), Fibronectines (métabolisme), Humains, Intégrines alpha (génétique), Intégrines alpha (métabolisme), Laminine (métabolisme), Matrice extracellulaire (métabolisme), Morphogenèse (physiologie), Petit ARN interférent (génétique), Petit ARN interférent (métabolisme), Souris, Souris knockout, Vaisseaux lymphatiques (anatomie et histologie), Vaisseaux lymphatiques (malformations), Vaisseaux lymphatiques (métabolisme).
- MESH :
- anatomie et histologie : Vaisseaux lymphatiques.
- cytologie : Cellules endothéliales.
- génétique : Intégrines alpha, Petit ARN interférent.
- malformations : Vaisseaux lymphatiques.
- métabolisme : Antigènes CD31, Cellules endothéliales, Fibronectines, Intégrines alpha, Laminine, Matrice extracellulaire, Petit ARN interférent, Vaisseaux lymphatiques.
- physiologie : Morphogenèse.
- Animaux, Humains, Souris, Souris knockout.
English descriptors
- KwdEn :
- Animals, Antigens, CD31 (metabolism), Endothelial Cells (cytology), Endothelial Cells (metabolism), Extracellular Matrix (metabolism), Fibronectins (metabolism), Humans, Integrin alpha Chains (genetics), Integrin alpha Chains (metabolism), Laminin (metabolism), Lymphatic Vessels (abnormalities), Lymphatic Vessels (anatomy & histology), Lymphatic Vessels (metabolism), Mice, Mice, Knockout, Morphogenesis (physiology), RNA, Small Interfering (genetics), RNA, Small Interfering (metabolism).
- MESH :
- chemical , genetics : Integrin alpha Chains, RNA, Small Interfering.
- chemical , metabolism : Antigens, CD31, Fibronectins, Integrin alpha Chains, Laminin, RNA, Small Interfering.
- abnormalities : Lymphatic Vessels.
- anatomy & histology : Lymphatic Vessels.
- cytology : Endothelial Cells.
- metabolism : Endothelial Cells, Extracellular Matrix, Lymphatic Vessels.
- physiology : Morphogenesis.
- Animals, Humans, Mice, Mice, Knockout.
Abstract
Dysfunction of lymphatic valves underlies human lymphedema, yet the
process of valve morphogenesis is poorly understood. Here, we show that during
embryogenesis lymphatic valve leaflet formation is initiated by upregulation of
integrin-α9 expression and deposition of its ligand, fibronectin-EIIIA
(FN-EIIIA), in the extracellular matrix. Endothelial cell specific deletion of
Url:
DOI: 10.1016/j.devcel.2009.06.017
PubMed: 19686679
PubMed Central: 2747264
Affiliations:
- Allemagne, Italie, Japon, Royaume-Uni, États-Unis
- District de Münster, Rhénanie-du-Nord-Westphalie
- Münster
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Le document en format XML
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during lymphatic valve morphogenesis</title><author><name sortKey="Bazigou, Eleni" sort="Bazigou, Eleni" uniqKey="Bazigou E" first="Eleni" last="Bazigou">Eleni Bazigou</name><affiliation wicri:level="1"><nlm:aff id="A1"> Lymphatic Development Laboratory, Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3PX, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea> Lymphatic Development Laboratory, Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3PX</wicri:regionArea><wicri:noRegion>London WC2A 3PX</wicri:noRegion></affiliation></author><author><name sortKey="Xie, Sherry" sort="Xie, Sherry" uniqKey="Xie S" first="Sherry" last="Xie">Sherry Xie</name><affiliation wicri:level="1"><nlm:aff id="A1"> Lymphatic Development Laboratory, Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3PX, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea> Lymphatic Development Laboratory, Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3PX</wicri:regionArea><wicri:noRegion>London WC2A 3PX</wicri:noRegion></affiliation></author><author><name sortKey="Chen, Chun" sort="Chen, Chun" uniqKey="Chen C" first="Chun" last="Chen">Chun Chen</name><affiliation wicri:level="1"><nlm:aff id="A2"> Lung Biology Center, UCSF, San Francisco CA 94143-2922, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea> Lung Biology Center, UCSF, San Francisco CA 94143-2922</wicri:regionArea><wicri:noRegion>San Francisco CA 94143-2922</wicri:noRegion></affiliation></author><author><name sortKey="Weston, Anne" sort="Weston, Anne" uniqKey="Weston A" first="Anne" last="Weston">Anne Weston</name><affiliation wicri:level="1"><nlm:aff id="A3"> Electron Microscopy Unit, Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3PX, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea> Electron Microscopy Unit, Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3PX</wicri:regionArea><wicri:noRegion>London WC2A 3PX</wicri:noRegion></affiliation></author><author><name sortKey="Miura, Naoyuki" sort="Miura, Naoyuki" uniqKey="Miura N" first="Naoyuki" last="Miura">Naoyuki Miura</name><affiliation wicri:level="1"><nlm:aff id="A4"> Department of Biochemistry, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea> Department of Biochemistry, Hamamatsu University School of Medicine, Hamamatsu 431-3192</wicri:regionArea><wicri:noRegion>Hamamatsu 431-3192</wicri:noRegion></affiliation></author><author><name sortKey="Sorokin, Lydia" sort="Sorokin, Lydia" uniqKey="Sorokin L" first="Lydia" last="Sorokin">Lydia Sorokin</name><affiliation wicri:level="3"><nlm:aff id="A5"> Institute for Physiological Chemistry and Pathobiochemistry, Münster University, 48149 Münster, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea> Institute for Physiological Chemistry and Pathobiochemistry, Münster University, 48149 Münster</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Münster</region><settlement type="city">Münster</settlement></placeName></affiliation></author><author><name sortKey="Adams, Ralf" sort="Adams, Ralf" uniqKey="Adams R" first="Ralf" last="Adams">Ralf Adams</name><affiliation wicri:level="1"><nlm:aff id="A6"> Vascular Development Laboratory, Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3PX, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea> Vascular Development Laboratory, Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3PX</wicri:regionArea><wicri:noRegion>London WC2A 3PX</wicri:noRegion></affiliation><affiliation wicri:level="3"><nlm:aff id="A7"> Max–Planck–Institute for Molecular Biomedicine, Department of Tissue Morphogenesis, and University of Münster, Faculty of Medicine, 48149 Münster, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea> Max–Planck–Institute for Molecular Biomedicine, Department of Tissue Morphogenesis, and University of Münster, Faculty of Medicine, 48149 Münster</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Münster</region><settlement type="city">Münster</settlement></placeName></affiliation></author><author><name sortKey="Muro, Andres F" sort="Muro, Andres F" uniqKey="Muro A" first="Andrés F." last="Muro">Andrés F. Muro</name><affiliation wicri:level="1"><nlm:aff id="A8"> International Centre for Genetic Engineering and Biotechnology, 34012 Trieste, Italy</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea> International Centre for Genetic Engineering and Biotechnology, 34012 Trieste</wicri:regionArea><wicri:noRegion>34012 Trieste</wicri:noRegion></affiliation></author><author><name sortKey="Sheppard, Dean" sort="Sheppard, Dean" uniqKey="Sheppard D" first="Dean" last="Sheppard">Dean Sheppard</name><affiliation wicri:level="1"><nlm:aff id="A2"> Lung Biology Center, UCSF, San Francisco CA 94143-2922, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea> Lung Biology Center, UCSF, San Francisco CA 94143-2922</wicri:regionArea><wicri:noRegion>San Francisco CA 94143-2922</wicri:noRegion></affiliation></author><author><name sortKey="Makinen, Taija" sort="Makinen, Taija" uniqKey="Makinen T" first="Taija" last="Makinen">Taija Makinen</name><affiliation wicri:level="1"><nlm:aff id="A1"> Lymphatic Development Laboratory, Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3PX, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea> Lymphatic Development Laboratory, Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3PX</wicri:regionArea><wicri:noRegion>London WC2A 3PX</wicri:noRegion></affiliation></author></analytic><series><title level="j">Developmental cell</title><idno type="ISSN">1534-5807</idno><idno type="eISSN">1878-1551</idno><imprint><date when="2009">2009</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Antigens, CD31 (metabolism)</term><term>Endothelial Cells (cytology)</term><term>Endothelial Cells (metabolism)</term><term>Extracellular Matrix (metabolism)</term><term>Fibronectins (metabolism)</term><term>Humans</term><term>Integrin alpha Chains (genetics)</term><term>Integrin alpha Chains (metabolism)</term><term>Laminin (metabolism)</term><term>Lymphatic Vessels (abnormalities)</term><term>Lymphatic Vessels (anatomy & histology)</term><term>Lymphatic Vessels (metabolism)</term><term>Mice</term><term>Mice, Knockout</term><term>Morphogenesis (physiology)</term><term>RNA, Small Interfering (genetics)</term><term>RNA, Small Interfering (metabolism)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Antigènes CD31 (métabolisme)</term><term>Cellules endothéliales (cytologie)</term><term>Cellules endothéliales (métabolisme)</term><term>Fibronectines (métabolisme)</term><term>Humains</term><term>Intégrines alpha (génétique)</term><term>Intégrines alpha (métabolisme)</term><term>Laminine (métabolisme)</term><term>Matrice extracellulaire (métabolisme)</term><term>Morphogenèse (physiologie)</term><term>Petit ARN interférent (génétique)</term><term>Petit ARN interférent (métabolisme)</term><term>Souris</term><term>Souris knockout</term><term>Vaisseaux lymphatiques (anatomie et histologie)</term><term>Vaisseaux lymphatiques (malformations)</term><term>Vaisseaux lymphatiques (métabolisme)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Integrin alpha Chains</term><term>RNA, Small Interfering</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Antigens, CD31</term><term>Fibronectins</term><term>Integrin alpha Chains</term><term>Laminin</term><term>RNA, Small Interfering</term></keywords><keywords scheme="MESH" qualifier="abnormalities" xml:lang="en"><term>Lymphatic Vessels</term></keywords><keywords scheme="MESH" qualifier="anatomie et histologie" xml:lang="fr"><term>Vaisseaux lymphatiques</term></keywords><keywords scheme="MESH" qualifier="anatomy & histology" xml:lang="en"><term>Lymphatic Vessels</term></keywords><keywords scheme="MESH" qualifier="cytologie" xml:lang="fr"><term>Cellules endothéliales</term></keywords><keywords scheme="MESH" qualifier="cytology" xml:lang="en"><term>Endothelial Cells</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Intégrines alpha</term><term>Petit ARN interférent</term></keywords><keywords scheme="MESH" qualifier="malformations" xml:lang="fr"><term>Vaisseaux lymphatiques</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Endothelial Cells</term><term>Extracellular Matrix</term><term>Lymphatic Vessels</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Antigènes CD31</term><term>Cellules endothéliales</term><term>Fibronectines</term><term>Intégrines alpha</term><term>Laminine</term><term>Matrice extracellulaire</term><term>Petit ARN interférent</term><term>Vaisseaux lymphatiques</term></keywords><keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Morphogenèse</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Morphogenesis</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Humans</term><term>Mice</term><term>Mice, Knockout</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Humains</term><term>Souris</term><term>Souris knockout</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><title>Summary</title><p id="P1">Dysfunction of lymphatic valves underlies human lymphedema, yet the
process of valve morphogenesis is poorly understood. Here, we show that during
embryogenesis lymphatic valve leaflet formation is initiated by upregulation of
integrin-α9 expression and deposition of its ligand, fibronectin-EIIIA
(FN-EIIIA), in the extracellular matrix. Endothelial cell specific deletion of
<italic>Itga9</italic> (encoding integrin-α9) in mouse embryos
results in the development of rudimentary valve leaflets, characterized by
disorganized FN matrix, short cusps and retrograde lymphatic flow. Similar
morphological and functional defects are observed in mice lacking the EIIIA
domain of FN. Mechanistically, we demonstrate that in primary human lymphatic
endothelial cells the integrin-α9-EIIIA interaction directly regulates
FN fibril assembly, which is essential for the formation of the extracellular
matrix core of valve leaflets. Our findings reveal an important role for
integrin-α9 signaling during lymphatic valve morphogenesis and implicate
it as a candidate gene for primary lymphedema caused by valve defects.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Alitalo, K" uniqKey="Alitalo K">K Alitalo</name></author><author><name sortKey="Tammela, T" uniqKey="Tammela T">T Tammela</name></author><author><name sortKey="Petrova, Tv" uniqKey="Petrova T">TV Petrova</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Armstrong, Ej" uniqKey="Armstrong E">EJ Armstrong</name></author><author><name sortKey="Bischoff, J" uniqKey="Bischoff J">J Bischoff</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Astrof, S" uniqKey="Astrof S">S Astrof</name></author><author><name sortKey="Crowley, D" uniqKey="Crowley D">D Crowley</name></author><author><name sortKey="George, El" uniqKey="George E">EL George</name></author><author><name sortKey="Fukuda, T" uniqKey="Fukuda T">T Fukuda</name></author><author><name 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uniqKey="Rosli C">C Rosli</name></author><author><name sortKey="Borsi, L" uniqKey="Borsi L">L Borsi</name></author><author><name sortKey="Neri, D" uniqKey="Neri D">D Neri</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wierzbicka Patynowski, I" uniqKey="Wierzbicka Patynowski I">I Wierzbicka-Patynowski</name></author><author><name sortKey="Mao, Y" uniqKey="Mao Y">Y Mao</name></author><author><name sortKey="Schwarzbauer, Je" uniqKey="Schwarzbauer J">JE Schwarzbauer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wierzbicka Patynowski, I" uniqKey="Wierzbicka Patynowski I">I Wierzbicka-Patynowski</name></author><author><name sortKey="Schwarzbauer, Je" uniqKey="Schwarzbauer J">JE Schwarzbauer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yokosaki, Y" uniqKey="Yokosaki Y">Y Yokosaki</name></author><author><name sortKey="Matsuura, N" uniqKey="Matsuura N">N Matsuura</name></author><author><name sortKey="Higashiyama, S" uniqKey="Higashiyama S">S Higashiyama</name></author><author><name sortKey="Murakami, I" uniqKey="Murakami I">I Murakami</name></author><author><name sortKey="Obara, M" uniqKey="Obara M">M Obara</name></author><author><name sortKey="Yamakido, M" uniqKey="Yamakido M">M Yamakido</name></author><author><name sortKey="Shigeto, N" uniqKey="Shigeto N">N Shigeto</name></author><author><name sortKey="Chen, J" uniqKey="Chen J">J Chen</name></author><author><name sortKey="Sheppard, D" uniqKey="Sheppard D">D Sheppard</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yokosaki, Y" uniqKey="Yokosaki Y">Y Yokosaki</name></author><author><name sortKey="Matsuura, N" uniqKey="Matsuura N">N Matsuura</name></author><author><name sortKey="Sasaki, T" uniqKey="Sasaki T">T Sasaki</name></author><author><name sortKey="Murakami, I" uniqKey="Murakami I">I Murakami</name></author><author><name sortKey="Schneider, H" uniqKey="Schneider H">H Schneider</name></author><author><name sortKey="Higashiyama, S" uniqKey="Higashiyama S">S Higashiyama</name></author><author><name sortKey="Saitoh, Y" uniqKey="Saitoh Y">Y Saitoh</name></author><author><name sortKey="Yamakido, M" uniqKey="Yamakido M">M Yamakido</name></author><author><name sortKey="Taooka, Y" uniqKey="Taooka Y">Y Taooka</name></author><author><name sortKey="Sheppard, D" uniqKey="Sheppard D">D Sheppard</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhong, C" uniqKey="Zhong C">C Zhong</name></author><author><name sortKey="Chrzanowska Wodnicka, M" uniqKey="Chrzanowska Wodnicka M">M Chrzanowska-Wodnicka</name></author><author><name sortKey="Brown, J" uniqKey="Brown J">J Brown</name></author><author><name sortKey="Shaub, A" uniqKey="Shaub A">A Shaub</name></author><author><name sortKey="Belkin, Am" uniqKey="Belkin A">AM Belkin</name></author><author><name sortKey="Burridge, K" uniqKey="Burridge K">K Burridge</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Allemagne</li><li>Italie</li><li>Japon</li><li>Royaume-Uni</li><li>États-Unis</li></country><region><li>District de Münster</li><li>Rhénanie-du-Nord-Westphalie</li></region><settlement><li>Münster</li></settlement></list><tree><country name="Royaume-Uni"><noRegion><name sortKey="Bazigou, Eleni" sort="Bazigou, Eleni" uniqKey="Bazigou E" first="Eleni" last="Bazigou">Eleni Bazigou</name></noRegion><name sortKey="Adams, Ralf" sort="Adams, Ralf" uniqKey="Adams R" first="Ralf" last="Adams">Ralf Adams</name><name sortKey="Makinen, Taija" sort="Makinen, Taija" uniqKey="Makinen T" first="Taija" last="Makinen">Taija Makinen</name><name sortKey="Weston, Anne" sort="Weston, Anne" uniqKey="Weston A" first="Anne" last="Weston">Anne Weston</name><name sortKey="Xie, Sherry" sort="Xie, Sherry" uniqKey="Xie S" first="Sherry" last="Xie">Sherry Xie</name></country><country name="États-Unis"><noRegion><name sortKey="Chen, Chun" sort="Chen, Chun" uniqKey="Chen C" first="Chun" last="Chen">Chun Chen</name></noRegion><name sortKey="Sheppard, Dean" sort="Sheppard, Dean" uniqKey="Sheppard D" first="Dean" last="Sheppard">Dean Sheppard</name></country><country name="Japon"><noRegion><name sortKey="Miura, Naoyuki" sort="Miura, Naoyuki" uniqKey="Miura N" first="Naoyuki" last="Miura">Naoyuki Miura</name></noRegion></country><country name="Allemagne"><region name="Rhénanie-du-Nord-Westphalie"><name sortKey="Sorokin, Lydia" sort="Sorokin, Lydia" uniqKey="Sorokin L" first="Lydia" last="Sorokin">Lydia Sorokin</name></region><name sortKey="Adams, Ralf" sort="Adams, Ralf" uniqKey="Adams R" first="Ralf" last="Adams">Ralf Adams</name></country><country name="Italie"><noRegion><name sortKey="Muro, Andres F" sort="Muro, Andres F" uniqKey="Muro A" first="Andrés F." last="Muro">Andrés F. 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