Vascular endothelial growth factor C is required for sprouting of the first lymphatic vessels from embryonic veins
Identifieur interne : 008904 ( Main/Exploration ); précédent : 008903; suivant : 008905Vascular endothelial growth factor C is required for sprouting of the first lymphatic vessels from embryonic veins
Auteurs : Marika J. Karkkainen [Finlande] ; Paula Haiko [Finlande] ; Kirsi Sainio [Finlande] ; Juha Partanen [Finlande] ; Jussi Taipale [Finlande] ; Tatiana V. Petrova [Finlande] ; Michael Jeltsch [Finlande] ; David G. Jackson [Royaume-Uni] ; Marja Talikka [Finlande] ; Heikki Rauvala [Finlande] ; Christer Betsholtz [Suède] ; Kari Alitalo [Finlande]Source :
- Nature Immunology [ 1529-2908 ] ; 2004-01.
Descripteurs français
- KwdFr :
- Animaux, Développement embryonnaire et foetal (génétique), Développement embryonnaire et foetal (physiologie), Facteur de croissance endothéliale vasculaire de type C (déficit), Facteur de croissance endothéliale vasculaire de type C (génétique), Facteur de croissance endothéliale vasculaire de type C (physiologie), Femelle, Immunohistochimie, Lymphangiogenèse (génétique), Lymphangiogenèse (physiologie), Lymphoedème (physiopathologie), Microscopie de fluorescence, Mâle, Récepteur-3 au facteur croissance endothéliale vasculaire (génétique), Récepteur-3 au facteur croissance endothéliale vasculaire (physiologie), Récepteurs aux facteurs de croissance endothéliale vasculaire (physiologie), Souris, Souris de lignée ICR, Souris knockout, Vaisseaux lymphatiques (embryologie).
- MESH :
- déficit : Facteur de croissance endothéliale vasculaire de type C.
- embryologie : Vaisseaux lymphatiques.
- génétique : Développement embryonnaire et foetal, Facteur de croissance endothéliale vasculaire de type C, Lymphangiogenèse, Récepteur-3 au facteur croissance endothéliale vasculaire.
- physiologie : Développement embryonnaire et foetal, Facteur de croissance endothéliale vasculaire de type C, Lymphangiogenèse, Récepteur-3 au facteur croissance endothéliale vasculaire, Récepteurs aux facteurs de croissance endothéliale vasculaire.
- physiopathologie : Lymphoedème.
- Animaux, Femelle, Immunohistochimie, Microscopie de fluorescence, Mâle, Souris, Souris de lignée ICR, Souris knockout.
English descriptors
- KwdEn :
- Animals, Embryonic and Fetal Development (genetics), Embryonic and Fetal Development (physiology), Female, Immunohistochemistry, Lymphangiogenesis (genetics), Lymphangiogenesis (physiology), Lymphatic Vessels (embryology), Lymphedema (physiopathology), Male, Mice, Mice, Inbred ICR, Mice, Knockout, Microscopy, Fluorescence, Receptors, Vascular Endothelial Growth Factor (physiology), Vascular Endothelial Growth Factor C (deficiency), Vascular Endothelial Growth Factor C (genetics), Vascular Endothelial Growth Factor C (physiology), Vascular Endothelial Growth Factor Receptor-3 (genetics), Vascular Endothelial Growth Factor Receptor-3 (physiology).
- MESH :
- chemical , deficiency : Vascular Endothelial Growth Factor C.
- chemical , genetics : Vascular Endothelial Growth Factor C, Vascular Endothelial Growth Factor Receptor-3.
- chemical , physiology : Receptors, Vascular Endothelial Growth Factor, Vascular Endothelial Growth Factor C, Vascular Endothelial Growth Factor Receptor-3.
- embryology : Lymphatic Vessels.
- genetics : Embryonic and Fetal Development, Lymphangiogenesis.
- physiology : Embryonic and Fetal Development, Lymphangiogenesis.
- physiopathology : Lymphedema.
- Animals, Female, Immunohistochemistry, Male, Mice, Mice, Inbred ICR, Mice, Knockout, Microscopy, Fluorescence.
Abstract
Lymphatic vessels are essential for immune surveillance, tissue fluid homeostasis and fat absorption. Defects in lymphatic vessel formation or function cause lymphedema. Here we show that the vascular endothelial growth factor C (VEGF-C) is required for the initial steps in lymphatic development. In Vegfc/ mice, endothelial cells commit to the lymphatic lineage but do not sprout to form lymph vessels. Sprouting was rescued by VEGF-C and VEGF-D but not by VEGF, indicating VEGF receptor 3 specificity. The lack of lymphatic vessels resulted in prenatal death due to fluid accumulation in tissues, and Vegfc+/ mice developed cutaneous lymphatic hypoplasia and lymphedema. Our results indicate that VEGF-C is the paracrine factor essential for lymphangiogenesis, and show that both Vegfc alleles are required for normal lymphatic development.
Url:
DOI: 10.1038/ni1013
Affiliations:
- Finlande, Royaume-Uni, Suède
- Angleterre, Oxfordshire, Uusimaa
- Helsinki, Oxford
- Université d'Helsinki
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Karkkainen</name><affiliation wicri:level="1"><country xml:lang="fr">Finlande</country><wicri:regionArea>Molecular/Cancer Biology Laboratory and Ludwig Institute for Cancer Research, Haartman Institute and Helsinki University Hospital, Biomedicum Helsinki, University of Helsinki, PO Box 63, 00014 Helsinki</wicri:regionArea><wicri:noRegion>00014 Helsinki</wicri:noRegion></affiliation></author><author><name sortKey="Haiko, Paula" sort="Haiko, Paula" uniqKey="Haiko P" first="Paula" last="Haiko">Paula Haiko</name><affiliation wicri:level="1"><country xml:lang="fr">Finlande</country><wicri:regionArea>Molecular/Cancer Biology Laboratory and Ludwig Institute for Cancer Research, Haartman Institute and Helsinki University Hospital, Biomedicum Helsinki, University of Helsinki, PO Box 63, 00014 Helsinki</wicri:regionArea><wicri:noRegion>00014 Helsinki</wicri:noRegion></affiliation></author><author><name sortKey="Sainio, Kirsi" sort="Sainio, Kirsi" uniqKey="Sainio K" first="Kirsi" last="Sainio">Kirsi Sainio</name><affiliation wicri:level="1"><country xml:lang="fr">Finlande</country><wicri:regionArea>Institute of Biomedicine, Developmental Biology, Biomedicum Helsinki and HUCH-diagnostics, PO Box 400, 00029 Helsinki</wicri:regionArea><wicri:noRegion>00029 Helsinki</wicri:noRegion></affiliation></author><author><name sortKey="Partanen, Juha" sort="Partanen, Juha" uniqKey="Partanen J" first="Juha" last="Partanen">Juha Partanen</name><affiliation wicri:level="4"><country xml:lang="fr">Finlande</country><wicri:regionArea>Institute of Biotechnology, University of Helsinki, PO Box 56, 00014 Helsinki</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="Taipale, Jussi" sort="Taipale, Jussi" uniqKey="Taipale J" first="Jussi" last="Taipale">Jussi Taipale</name><affiliation wicri:level="1"><country xml:lang="fr">Finlande</country><wicri:regionArea>Molecular/Cancer Biology Laboratory and Ludwig Institute for Cancer Research, Haartman Institute and Helsinki University Hospital, Biomedicum Helsinki, University of Helsinki, PO Box 63, 00014 Helsinki</wicri:regionArea><wicri:noRegion>00014 Helsinki</wicri:noRegion></affiliation></author><author><name sortKey="Petrova, Tatiana V" sort="Petrova, Tatiana V" uniqKey="Petrova T" first="Tatiana V" last="Petrova">Tatiana V. Petrova</name><affiliation wicri:level="1"><country xml:lang="fr">Finlande</country><wicri:regionArea>Molecular/Cancer Biology Laboratory and Ludwig Institute for Cancer Research, Haartman Institute and Helsinki University Hospital, Biomedicum Helsinki, University of Helsinki, PO Box 63, 00014 Helsinki</wicri:regionArea><wicri:noRegion>00014 Helsinki</wicri:noRegion></affiliation></author><author><name sortKey="Jeltsch, Michael" sort="Jeltsch, Michael" uniqKey="Jeltsch M" first="Michael" last="Jeltsch">Michael Jeltsch</name><affiliation wicri:level="1"><country xml:lang="fr">Finlande</country><wicri:regionArea>Molecular/Cancer Biology Laboratory and Ludwig Institute for Cancer Research, Haartman Institute and Helsinki University Hospital, Biomedicum Helsinki, University of Helsinki, PO Box 63, 00014 Helsinki</wicri:regionArea><wicri:noRegion>00014 Helsinki</wicri:noRegion></affiliation></author><author><name sortKey="Jackson, David G" sort="Jackson, David G" uniqKey="Jackson D" first="David G" last="Jackson">David G. Jackson</name><affiliation wicri:level="3"><country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country><wicri:regionArea>MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford</wicri:regionArea><placeName><settlement type="city">Oxford</settlement><region type="country">Angleterre</region><region type="comté" nuts="2">Oxfordshire</region></placeName></affiliation></author><author><name sortKey="Talikka, Marja" sort="Talikka, Marja" uniqKey="Talikka M" first="Marja" last="Talikka">Marja Talikka</name><affiliation wicri:level="4"><country xml:lang="fr">Finlande</country><wicri:regionArea>Neuroscience Center, University of Helsinki, PO Box 56, 00014 Helsinki</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="Rauvala, Heikki" sort="Rauvala, 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Alitalo</name><affiliation wicri:level="1"><country xml:lang="fr">Finlande</country><wicri:regionArea>Molecular/Cancer Biology Laboratory and Ludwig Institute for Cancer Research, Haartman Institute and Helsinki University Hospital, Biomedicum Helsinki, University of Helsinki, PO Box 63, 00014 Helsinki</wicri:regionArea><wicri:noRegion>00014 Helsinki</wicri:noRegion><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="1"><country wicri:rule="url">Finlande</country><placeName><settlement type="city">Helsinki</settlement><region type="région" nuts="2">Uusimaa</region></placeName><orgName type="university">Université d'Helsinki</orgName></affiliation></author></analytic><monogr></monogr><series><title level="j">Nature Immunology</title><idno type="ISSN">1529-2908</idno><imprint><publisher>Nature Publishing Group</publisher><date type="published" when="2004-01">2004-01</date><biblScope unit="volume">5</biblScope><biblScope unit="issue">1</biblScope><biblScope unit="page" from="74">74</biblScope><biblScope unit="page" to="80">80</biblScope></imprint><idno type="ISSN">1529-2908</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">1529-2908</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Embryonic and Fetal Development (genetics)</term><term>Embryonic and Fetal Development (physiology)</term><term>Female</term><term>Immunohistochemistry</term><term>Lymphangiogenesis (genetics)</term><term>Lymphangiogenesis (physiology)</term><term>Lymphatic Vessels (embryology)</term><term>Lymphedema (physiopathology)</term><term>Male</term><term>Mice</term><term>Mice, Inbred ICR</term><term>Mice, Knockout</term><term>Microscopy, Fluorescence</term><term>Receptors, Vascular Endothelial Growth Factor (physiology)</term><term>Vascular Endothelial Growth Factor C (deficiency)</term><term>Vascular Endothelial Growth Factor C (genetics)</term><term>Vascular Endothelial Growth Factor C (physiology)</term><term>Vascular Endothelial Growth Factor Receptor-3 (genetics)</term><term>Vascular Endothelial Growth Factor Receptor-3 (physiology)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Développement embryonnaire et foetal (génétique)</term><term>Développement embryonnaire et foetal (physiologie)</term><term>Facteur de croissance endothéliale vasculaire de type C (déficit)</term><term>Facteur de croissance endothéliale vasculaire de type C (génétique)</term><term>Facteur de croissance endothéliale vasculaire de type C (physiologie)</term><term>Femelle</term><term>Immunohistochimie</term><term>Lymphangiogenèse (génétique)</term><term>Lymphangiogenèse (physiologie)</term><term>Lymphoedème (physiopathologie)</term><term>Microscopie de fluorescence</term><term>Mâle</term><term>Récepteur-3 au facteur croissance endothéliale vasculaire (génétique)</term><term>Récepteur-3 au facteur croissance endothéliale vasculaire (physiologie)</term><term>Récepteurs aux facteurs de croissance endothéliale vasculaire (physiologie)</term><term>Souris</term><term>Souris de lignée ICR</term><term>Souris knockout</term><term>Vaisseaux lymphatiques (embryologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="deficiency" xml:lang="en"><term>Vascular Endothelial Growth Factor C</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Vascular Endothelial Growth Factor C</term><term>Vascular Endothelial Growth Factor Receptor-3</term></keywords><keywords scheme="MESH" type="chemical" qualifier="physiology" xml:lang="en"><term>Receptors, Vascular Endothelial Growth Factor</term><term>Vascular Endothelial Growth Factor C</term><term>Vascular Endothelial Growth Factor Receptor-3</term></keywords><keywords scheme="MESH" qualifier="déficit" xml:lang="fr"><term>Facteur de croissance endothéliale vasculaire de type C</term></keywords><keywords scheme="MESH" qualifier="embryologie" xml:lang="fr"><term>Vaisseaux lymphatiques</term></keywords><keywords scheme="MESH" qualifier="embryology" xml:lang="en"><term>Lymphatic Vessels</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Embryonic and Fetal Development</term><term>Lymphangiogenesis</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Développement embryonnaire et foetal</term><term>Facteur de croissance endothéliale vasculaire de type C</term><term>Lymphangiogenèse</term><term>Récepteur-3 au facteur croissance endothéliale vasculaire</term></keywords><keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Développement embryonnaire et foetal</term><term>Facteur de croissance endothéliale vasculaire de type C</term><term>Lymphangiogenèse</term><term>Récepteur-3 au facteur croissance endothéliale vasculaire</term><term>Récepteurs aux facteurs de croissance endothéliale vasculaire</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Embryonic and Fetal Development</term><term>Lymphangiogenesis</term></keywords><keywords scheme="MESH" qualifier="physiopathologie" xml:lang="fr"><term>Lymphoedème</term></keywords><keywords scheme="MESH" qualifier="physiopathology" xml:lang="en"><term>Lymphedema</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Female</term><term>Immunohistochemistry</term><term>Male</term><term>Mice</term><term>Mice, Inbred ICR</term><term>Mice, Knockout</term><term>Microscopy, Fluorescence</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Femelle</term><term>Immunohistochimie</term><term>Microscopie de fluorescence</term><term>Mâle</term><term>Souris</term><term>Souris de lignée ICR</term><term>Souris knockout</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="eng">Lymphatic vessels are essential for immune surveillance, tissue fluid homeostasis and fat absorption. Defects in lymphatic vessel formation or function cause lymphedema. Here we show that the vascular endothelial growth factor C (VEGF-C) is required for the initial steps in lymphatic development. In Vegfc/ mice, endothelial cells commit to the lymphatic lineage but do not sprout to form lymph vessels. Sprouting was rescued by VEGF-C and VEGF-D but not by VEGF, indicating VEGF receptor 3 specificity. The lack of lymphatic vessels resulted in prenatal death due to fluid accumulation in tissues, and Vegfc+/ mice developed cutaneous lymphatic hypoplasia and lymphedema. Our results indicate that VEGF-C is the paracrine factor essential for lymphangiogenesis, and show that both Vegfc alleles are required for normal lymphatic development.</div></front></TEI><affiliations><list><country><li>Finlande</li><li>Royaume-Uni</li><li>Suède</li></country><region><li>Angleterre</li><li>Oxfordshire</li><li>Uusimaa</li></region><settlement><li>Helsinki</li><li>Oxford</li></settlement><orgName><li>Université d'Helsinki</li></orgName></list><tree><country name="Finlande"><noRegion><name sortKey="Karkkainen, Marika J" sort="Karkkainen, Marika J" uniqKey="Karkkainen M" first="Marika J" last="Karkkainen">Marika J. Karkkainen</name></noRegion><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><name sortKey="Haiko, Paula" sort="Haiko, Paula" uniqKey="Haiko P" first="Paula" last="Haiko">Paula Haiko</name><name sortKey="Jeltsch, Michael" sort="Jeltsch, Michael" uniqKey="Jeltsch M" first="Michael" last="Jeltsch">Michael Jeltsch</name><name sortKey="Partanen, Juha" sort="Partanen, Juha" uniqKey="Partanen J" first="Juha" last="Partanen">Juha Partanen</name><name sortKey="Petrova, Tatiana V" sort="Petrova, Tatiana V" uniqKey="Petrova T" first="Tatiana V" last="Petrova">Tatiana V. Petrova</name><name sortKey="Rauvala, Heikki" sort="Rauvala, Heikki" uniqKey="Rauvala H" first="Heikki" last="Rauvala">Heikki Rauvala</name><name sortKey="Sainio, Kirsi" sort="Sainio, Kirsi" uniqKey="Sainio K" first="Kirsi" last="Sainio">Kirsi Sainio</name><name sortKey="Taipale, Jussi" sort="Taipale, Jussi" uniqKey="Taipale J" first="Jussi" last="Taipale">Jussi Taipale</name><name sortKey="Talikka, Marja" sort="Talikka, Marja" uniqKey="Talikka M" first="Marja" last="Talikka">Marja Talikka</name></country><country name="Royaume-Uni"><region name="Angleterre"><name sortKey="Jackson, David G" sort="Jackson, David G" uniqKey="Jackson D" first="David G" last="Jackson">David G. Jackson</name></region></country><country name="Suède"><noRegion><name sortKey="Betsholtz, Christer" sort="Betsholtz, Christer" uniqKey="Betsholtz C" first="Christer" last="Betsholtz">Christer Betsholtz</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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