Ccbe1 regulates Vegfc-mediated induction of Vegfr3 signaling during embryonic lymphangiogenesis.
Identifieur interne : 002C71 ( Main/Exploration ); précédent : 002C70; suivant : 002C72Ccbe1 regulates Vegfc-mediated induction of Vegfr3 signaling during embryonic lymphangiogenesis.
Auteurs : Ludovic Le Guen [Australie] ; Terhi Karpanen ; Dörte Schulte ; Nicole C. Harris ; Katarzyna Koltowska ; Guy Roukens ; Neil I. Bower ; Andreas Van Impel ; Steven A. Stacker ; Marc G. Achen ; Stefan Schulte-Merker ; Benjamin M. HoganSource :
- Development (Cambridge, England) [ 1477-9129 ] ; 2014.
Descripteurs français
- KwdFr :
- ADN (génétique), Animaux, Danio zébré (embryologie), Danio zébré (génétique), Danio zébré (métabolisme), Données de séquences moléculaires, Facteur de croissance endothéliale vasculaire de type C (génétique), Facteur de croissance endothéliale vasculaire de type C (métabolisme), Humains, Lymphangiogenèse (génétique), Lymphangiogenèse (physiologie), Mutation ponctuelle, Protéines de poisson-zèbre (génétique), Protéines de poisson-zèbre (métabolisme), Récepteur-3 au facteur croissance endothéliale vasculaire (génétique), Récepteur-3 au facteur croissance endothéliale vasculaire (métabolisme), Régulation de l'expression des gènes au cours du développement, Similitude de séquences d'acides aminés, Similitude de séquences d'acides nucléiques, Souris, Substitution d'acide aminé, Système de signalisation des MAP kinases, Séquence d'acides aminés, Séquence nucléotidique, Transduction du signal.
- MESH :
- embryologie : Danio zébré.
- génétique : ADN, Danio zébré, Facteur de croissance endothéliale vasculaire de type C, Lymphangiogenèse, Protéines de poisson-zèbre, Récepteur-3 au facteur croissance endothéliale vasculaire.
- métabolisme : Danio zébré, Facteur de croissance endothéliale vasculaire de type C, Protéines de poisson-zèbre, Récepteur-3 au facteur croissance endothéliale vasculaire.
- physiologie : Lymphangiogenèse.
- Animaux, Données de séquences moléculaires, Humains, Mutation ponctuelle, Régulation de l'expression des gènes au cours du développement, Similitude de séquences d'acides aminés, Similitude de séquences d'acides nucléiques, Souris, Substitution d'acide aminé, Système de signalisation des MAP kinases, Séquence d'acides aminés, Séquence nucléotidique, Transduction du signal.
English descriptors
- KwdEn :
- Amino Acid Sequence, Amino Acid Substitution, Animals, Base Sequence, DNA (genetics), Gene Expression Regulation, Developmental, Humans, Lymphangiogenesis (genetics), Lymphangiogenesis (physiology), MAP Kinase Signaling System, Mice, Molecular Sequence Data, Point Mutation, Sequence Homology, Amino Acid, Sequence Homology, Nucleic Acid, Signal Transduction, Vascular Endothelial Growth Factor C (genetics), Vascular Endothelial Growth Factor C (metabolism), Vascular Endothelial Growth Factor Receptor-3 (genetics), Vascular Endothelial Growth Factor Receptor-3 (metabolism), Zebrafish (embryology), Zebrafish (genetics), Zebrafish (metabolism), Zebrafish Proteins (genetics), Zebrafish Proteins (metabolism).
- MESH :
- chemical , genetics : DNA, Vascular Endothelial Growth Factor C, Vascular Endothelial Growth Factor Receptor-3, Zebrafish Proteins.
- embryology : Zebrafish.
- genetics : Lymphangiogenesis, Zebrafish.
- chemical , metabolism : Vascular Endothelial Growth Factor C, Vascular Endothelial Growth Factor Receptor-3, Zebrafish, Zebrafish Proteins.
- physiology : Lymphangiogenesis.
- Amino Acid Sequence, Amino Acid Substitution, Animals, Base Sequence, Gene Expression Regulation, Developmental, Humans, MAP Kinase Signaling System, Mice, Molecular Sequence Data, Point Mutation, Sequence Homology, Amino Acid, Sequence Homology, Nucleic Acid, Signal Transduction.
Abstract
The VEGFC/VEGFR3 signaling pathway is essential for lymphangiogenesis (the formation of lymphatic vessels from pre-existing vasculature) during embryonic development, tissue regeneration and tumor progression. The recently identified secreted protein CCBE1 is indispensible for lymphangiogenesis during development. The role of CCBE1 orthologs is highly conserved in zebrafish, mice and humans with mutations in CCBE1 causing generalized lymphatic dysplasia and lymphedema (Hennekam syndrome). To date, the mechanism by which CCBE1 acts remains unknown. Here, we find that ccbe1 genetically interacts with both vegfc and vegfr3 in zebrafish. In the embryo, phenotypes driven by increased Vegfc are suppressed in the absence of Ccbe1, and Vegfc-driven sprouting is enhanced by local Ccbe1 overexpression. Moreover, Vegfc- and Vegfr3-dependent Erk signaling is impaired in the absence of Ccbe1. Finally, CCBE1 is capable of upregulating the levels of fully processed, mature VEGFC in vitro and the overexpression of mature VEGFC rescues ccbe1 loss-of-function phenotypes in zebrafish. Taken together, these data identify Ccbe1 as a crucial component of the Vegfc/Vegfr3 pathway in the embryo.
DOI: 10.1242/dev.100495
PubMed: 24523457
Affiliations:
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Harris</name></author><author><name sortKey="Koltowska, Katarzyna" sort="Koltowska, Katarzyna" uniqKey="Koltowska K" first="Katarzyna" last="Koltowska">Katarzyna Koltowska</name></author><author><name sortKey="Roukens, Guy" sort="Roukens, Guy" uniqKey="Roukens G" first="Guy" last="Roukens">Guy Roukens</name></author><author><name sortKey="Bower, Neil I" sort="Bower, Neil I" uniqKey="Bower N" first="Neil I" last="Bower">Neil I. Bower</name></author><author><name sortKey="Van Impel, Andreas" sort="Van Impel, Andreas" uniqKey="Van Impel A" first="Andreas" last="Van Impel">Andreas Van Impel</name></author><author><name sortKey="Stacker, Steven A" sort="Stacker, Steven A" uniqKey="Stacker S" first="Steven A" last="Stacker">Steven A. Stacker</name></author><author><name sortKey="Achen, Marc G" sort="Achen, Marc G" uniqKey="Achen M" first="Marc G" last="Achen">Marc G. Achen</name></author><author><name sortKey="Schulte Merker, Stefan" sort="Schulte Merker, Stefan" uniqKey="Schulte Merker S" first="Stefan" last="Schulte-Merker">Stefan Schulte-Merker</name></author><author><name sortKey="Hogan, Benjamin M" sort="Hogan, Benjamin M" uniqKey="Hogan B" first="Benjamin M" last="Hogan">Benjamin M. Hogan</name></author></analytic><series><title level="j">Development (Cambridge, England)</title><idno type="eISSN">1477-9129</idno><imprint><date when="2014" type="published">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Amino Acid Sequence</term><term>Amino Acid Substitution</term><term>Animals</term><term>Base Sequence</term><term>DNA (genetics)</term><term>Gene Expression Regulation, Developmental</term><term>Humans</term><term>Lymphangiogenesis (genetics)</term><term>Lymphangiogenesis (physiology)</term><term>MAP Kinase Signaling System</term><term>Mice</term><term>Molecular Sequence Data</term><term>Point Mutation</term><term>Sequence Homology, Amino Acid</term><term>Sequence Homology, Nucleic Acid</term><term>Signal Transduction</term><term>Vascular Endothelial Growth Factor C (genetics)</term><term>Vascular Endothelial Growth Factor C (metabolism)</term><term>Vascular Endothelial Growth Factor Receptor-3 (genetics)</term><term>Vascular Endothelial Growth Factor Receptor-3 (metabolism)</term><term>Zebrafish (embryology)</term><term>Zebrafish (genetics)</term><term>Zebrafish (metabolism)</term><term>Zebrafish Proteins (genetics)</term><term>Zebrafish Proteins (metabolism)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>ADN (génétique)</term><term>Animaux</term><term>Danio zébré (embryologie)</term><term>Danio zébré (génétique)</term><term>Danio zébré (métabolisme)</term><term>Données de séquences moléculaires</term><term>Facteur de croissance endothéliale vasculaire de type C (génétique)</term><term>Facteur de croissance endothéliale vasculaire de type C (métabolisme)</term><term>Humains</term><term>Lymphangiogenèse (génétique)</term><term>Lymphangiogenèse (physiologie)</term><term>Mutation ponctuelle</term><term>Protéines de poisson-zèbre (génétique)</term><term>Protéines de poisson-zèbre (métabolisme)</term><term>Récepteur-3 au facteur croissance endothéliale vasculaire (génétique)</term><term>Récepteur-3 au facteur croissance endothéliale vasculaire (métabolisme)</term><term>Régulation de l'expression des gènes au cours du développement</term><term>Similitude de séquences d'acides aminés</term><term>Similitude de séquences d'acides nucléiques</term><term>Souris</term><term>Substitution d'acide aminé</term><term>Système de signalisation des MAP kinases</term><term>Séquence d'acides aminés</term><term>Séquence nucléotidique</term><term>Transduction du signal</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>DNA</term><term>Vascular Endothelial Growth Factor C</term><term>Vascular Endothelial Growth Factor Receptor-3</term><term>Zebrafish Proteins</term></keywords><keywords scheme="MESH" qualifier="embryologie" xml:lang="fr"><term>Danio zébré</term></keywords><keywords scheme="MESH" qualifier="embryology" xml:lang="en"><term>Zebrafish</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Lymphangiogenesis</term><term>Zebrafish</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>ADN</term><term>Danio zébré</term><term>Facteur de croissance endothéliale vasculaire de type C</term><term>Lymphangiogenèse</term><term>Protéines de poisson-zèbre</term><term>Récepteur-3 au facteur croissance endothéliale vasculaire</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Vascular Endothelial Growth Factor C</term><term>Vascular Endothelial Growth Factor Receptor-3</term><term>Zebrafish</term><term>Zebrafish Proteins</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Danio zébré</term><term>Facteur de croissance endothéliale vasculaire de type C</term><term>Protéines de poisson-zèbre</term><term>Récepteur-3 au facteur croissance endothéliale vasculaire</term></keywords><keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Lymphangiogenèse</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Lymphangiogenesis</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Amino Acid Sequence</term><term>Amino Acid Substitution</term><term>Animals</term><term>Base Sequence</term><term>Gene Expression Regulation, Developmental</term><term>Humans</term><term>MAP Kinase Signaling System</term><term>Mice</term><term>Molecular Sequence Data</term><term>Point Mutation</term><term>Sequence Homology, Amino Acid</term><term>Sequence Homology, Nucleic Acid</term><term>Signal Transduction</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Données de séquences moléculaires</term><term>Humains</term><term>Mutation ponctuelle</term><term>Régulation de l'expression des gènes au cours du développement</term><term>Similitude de séquences d'acides aminés</term><term>Similitude de séquences d'acides nucléiques</term><term>Souris</term><term>Substitution d'acide aminé</term><term>Système de signalisation des MAP kinases</term><term>Séquence d'acides aminés</term><term>Séquence nucléotidique</term><term>Transduction du signal</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The VEGFC/VEGFR3 signaling pathway is essential for lymphangiogenesis (the formation of lymphatic vessels from pre-existing vasculature) during embryonic development, tissue regeneration and tumor progression. The recently identified secreted protein CCBE1 is indispensible for lymphangiogenesis during development. The role of CCBE1 orthologs is highly conserved in zebrafish, mice and humans with mutations in CCBE1 causing generalized lymphatic dysplasia and lymphedema (Hennekam syndrome). To date, the mechanism by which CCBE1 acts remains unknown. Here, we find that ccbe1 genetically interacts with both vegfc and vegfr3 in zebrafish. In the embryo, phenotypes driven by increased Vegfc are suppressed in the absence of Ccbe1, and Vegfc-driven sprouting is enhanced by local Ccbe1 overexpression. Moreover, Vegfc- and Vegfr3-dependent Erk signaling is impaired in the absence of Ccbe1. Finally, CCBE1 is capable of upregulating the levels of fully processed, mature VEGFC in vitro and the overexpression of mature VEGFC rescues ccbe1 loss-of-function phenotypes in zebrafish. Taken together, these data identify Ccbe1 as a crucial component of the Vegfc/Vegfr3 pathway in the embryo.</div></front></TEI><affiliations><list><country><li>Australie</li></country></list><tree><noCountry><name sortKey="Achen, Marc G" sort="Achen, Marc G" uniqKey="Achen M" first="Marc G" last="Achen">Marc G. Achen</name><name sortKey="Bower, Neil I" sort="Bower, Neil I" uniqKey="Bower N" first="Neil I" last="Bower">Neil I. Bower</name><name sortKey="Harris, Nicole C" sort="Harris, Nicole C" uniqKey="Harris N" first="Nicole C" last="Harris">Nicole C. Harris</name><name sortKey="Hogan, Benjamin M" sort="Hogan, Benjamin M" uniqKey="Hogan B" first="Benjamin M" last="Hogan">Benjamin M. Hogan</name><name sortKey="Karpanen, Terhi" sort="Karpanen, Terhi" uniqKey="Karpanen T" first="Terhi" last="Karpanen">Terhi Karpanen</name><name sortKey="Koltowska, Katarzyna" sort="Koltowska, Katarzyna" uniqKey="Koltowska K" first="Katarzyna" last="Koltowska">Katarzyna Koltowska</name><name sortKey="Roukens, Guy" sort="Roukens, Guy" uniqKey="Roukens G" first="Guy" last="Roukens">Guy Roukens</name><name sortKey="Schulte Merker, Stefan" sort="Schulte Merker, Stefan" uniqKey="Schulte Merker S" first="Stefan" last="Schulte-Merker">Stefan Schulte-Merker</name><name sortKey="Schulte, Dorte" sort="Schulte, Dorte" uniqKey="Schulte D" first="Dörte" last="Schulte">Dörte Schulte</name><name sortKey="Stacker, Steven A" sort="Stacker, Steven A" uniqKey="Stacker S" first="Steven A" last="Stacker">Steven A. Stacker</name><name sortKey="Van Impel, Andreas" sort="Van Impel, Andreas" uniqKey="Van Impel A" first="Andreas" last="Van Impel">Andreas Van Impel</name></noCountry><country name="Australie"><noRegion><name sortKey="Le Guen, Ludovic" sort="Le Guen, Ludovic" uniqKey="Le Guen L" first="Ludovic" last="Le Guen">Ludovic Le Guen</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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