Sox18 induces development of the lymphatic vasculature in mice.
Identifieur interne : 006934 ( Main/Exploration ); précédent : 006933; suivant : 006935Sox18 induces development of the lymphatic vasculature in mice.
Auteurs : Mathias François [Australie] ; Andrea Caprini ; Brett Hosking ; Fabrizio Orsenigo ; Dagmar Wilhelm ; Catherine Browne ; Karri Paavonen ; Tara Karnezis ; Ramin Shayan ; Meredith Downes ; Tara Davidson ; Desmond Tutt ; Kathryn S E. Cheah ; Steven A. Stacker ; George E O. Muscat ; Marc G. Achen ; Elisabetta Dejana ; Peter KoopmanSource :
- Nature [ 1476-4687 ] ; 2008.
Descripteurs français
- KwdFr :
- Animaux, Cellules cultivées, Cellules endothéliales (cytologie), Cellules endothéliales (métabolisme), Différenciation cellulaire, Facteurs de transcription SOX-F (déficit), Facteurs de transcription SOX-F (génétique), Facteurs de transcription SOX-F (métabolisme), Femelle, Hypotrichose (génétique), Lymphangiogenèse, Marqueurs biologiques (analyse), Mouvement cellulaire, Mâle, Oedème (génétique), Protéines suppresseurs de tumeurs (génétique), Protéines à homéodomaine (génétique), Récepteur-3 au facteur croissance endothéliale vasculaire (génétique), Régions promotrices (génétique) (génétique), Régulation de l'expression des gènes au cours du développement, Souris, Souris de lignée C57BL, Souris de lignée CBA, Télangiectasie (génétique), Vaisseaux lymphatiques (cytologie), Vaisseaux lymphatiques (embryologie), Vaisseaux lymphatiques (métabolisme), Veines (cytologie), Éphrine B2 (génétique).
- MESH :
- analyse : Marqueurs biologiques.
- cytologie : Cellules endothéliales, Vaisseaux lymphatiques, Veines.
- déficit : Facteurs de transcription SOX-F.
- embryologie : Vaisseaux lymphatiques.
- génétique : Facteurs de transcription SOX-F, Hypotrichose, Oedème, Protéines suppresseurs de tumeurs, Protéines à homéodomaine, Récepteur-3 au facteur croissance endothéliale vasculaire, Régions promotrices (génétique), Télangiectasie, Éphrine B2.
- métabolisme : Cellules endothéliales, Facteurs de transcription SOX-F, Vaisseaux lymphatiques.
- Animaux, Cellules cultivées, Différenciation cellulaire, Femelle, Lymphangiogenèse, Mouvement cellulaire, Mâle, Régulation de l'expression des gènes au cours du développement, Souris, Souris de lignée C57BL, Souris de lignée CBA.
English descriptors
- KwdEn :
- Animals, Biomarkers (analysis), Cell Differentiation, Cell Movement, Cells, Cultured, Edema (genetics), Endothelial Cells (cytology), Endothelial Cells (metabolism), Ephrin-B2 (genetics), Female, Gene Expression Regulation, Developmental, Homeodomain Proteins (genetics), Hypotrichosis (genetics), Lymphangiogenesis, Lymphatic Vessels (cytology), Lymphatic Vessels (embryology), Lymphatic Vessels (metabolism), Male, Mice, Mice, Inbred C57BL, Mice, Inbred CBA, Promoter Regions, Genetic (genetics), SOXF Transcription Factors (deficiency), SOXF Transcription Factors (genetics), SOXF Transcription Factors (metabolism), Telangiectasis (genetics), Tumor Suppressor Proteins (genetics), Vascular Endothelial Growth Factor Receptor-3 (genetics), Veins (cytology).
- MESH :
- chemical , analysis : Biomarkers.
- cytology : Endothelial Cells, Lymphatic Vessels, Veins.
- chemical , deficiency : SOXF Transcription Factors.
- embryology : Lymphatic Vessels.
- genetics : Edema, Ephrin-B2, Homeodomain Proteins, Hypotrichosis, Promoter Regions, Genetic, SOXF Transcription Factors, Telangiectasis, Tumor Suppressor Proteins, Vascular Endothelial Growth Factor Receptor-3.
- metabolism : Endothelial Cells, Lymphatic Vessels, SOXF Transcription Factors.
- Animals, Cell Differentiation, Cell Movement, Cells, Cultured, Female, Gene Expression Regulation, Developmental, Lymphangiogenesis, Male, Mice, Mice, Inbred C57BL, Mice, Inbred CBA.
Abstract
The lymphatic system plays a key role in tissue fluid regulation and tumour metastasis, and lymphatic defects underlie many pathological states including lymphoedema, lymphangiectasia, lymphangioma and lymphatic dysplasia. However, the origins of the lymphatic system in the embryo, and the mechanisms that direct growth of the network of lymphatic vessels, remain unclear. Lymphatic vessels are thought to arise from endothelial precursor cells budding from the cardinal vein under the influence of the lymphatic hallmark gene Prox1 (prospero homeobox 1; ref. 4). Defects in the transcription factor gene SOX18 (SRY (sex determining region Y) box 18) cause lymphatic dysfunction in the human syndrome hypotrichosis-lymphoedema-telangiectasia, suggesting that Sox18 may also play a role in lymphatic development or function. Here we use molecular, cellular and genetic assays in mice to show that Sox18 acts as a molecular switch to induce differentiation of lymphatic endothelial cells. Sox18 is expressed in a subset of cardinal vein cells that later co-express Prox1 and migrate to form lymphatic vessels. Sox18 directly activates Prox1 transcription by binding to its proximal promoter. Overexpression of Sox18 in blood vascular endothelial cells induces them to express Prox1 and other lymphatic endothelial markers, while Sox18-null embryos show a complete blockade of lymphatic endothelial cell differentiation from the cardinal vein. Our findings demonstrate a critical role for Sox18 in developmental lymphangiogenesis, and suggest new avenues to investigate for therapeutic management of human lymphangiopathies.
DOI: 10.1038/nature07391
PubMed: 18931657
Affiliations:
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Le document en format XML
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Cheah</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="Muscat, George E O" sort="Muscat, George E O" uniqKey="Muscat G" first="George E O" last="Muscat">George E O. Muscat</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="Dejana, Elisabetta" sort="Dejana, Elisabetta" uniqKey="Dejana E" first="Elisabetta" last="Dejana">Elisabetta Dejana</name></author><author><name sortKey="Koopman, Peter" sort="Koopman, Peter" uniqKey="Koopman P" first="Peter" last="Koopman">Peter Koopman</name></author></analytic><series><title level="j">Nature</title><idno type="eISSN">1476-4687</idno><imprint><date when="2008" type="published">2008</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Biomarkers (analysis)</term><term>Cell Differentiation</term><term>Cell Movement</term><term>Cells, Cultured</term><term>Edema (genetics)</term><term>Endothelial Cells (cytology)</term><term>Endothelial Cells (metabolism)</term><term>Ephrin-B2 (genetics)</term><term>Female</term><term>Gene Expression Regulation, Developmental</term><term>Homeodomain Proteins (genetics)</term><term>Hypotrichosis (genetics)</term><term>Lymphangiogenesis</term><term>Lymphatic Vessels (cytology)</term><term>Lymphatic Vessels (embryology)</term><term>Lymphatic Vessels (metabolism)</term><term>Male</term><term>Mice</term><term>Mice, Inbred C57BL</term><term>Mice, Inbred CBA</term><term>Promoter Regions, Genetic (genetics)</term><term>SOXF Transcription Factors (deficiency)</term><term>SOXF Transcription Factors (genetics)</term><term>SOXF Transcription Factors (metabolism)</term><term>Telangiectasis (genetics)</term><term>Tumor Suppressor Proteins (genetics)</term><term>Vascular Endothelial Growth Factor Receptor-3 (genetics)</term><term>Veins (cytology)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Cellules cultivées</term><term>Cellules endothéliales (cytologie)</term><term>Cellules endothéliales (métabolisme)</term><term>Différenciation cellulaire</term><term>Facteurs de transcription SOX-F (déficit)</term><term>Facteurs de transcription SOX-F (génétique)</term><term>Facteurs de transcription SOX-F (métabolisme)</term><term>Femelle</term><term>Hypotrichose (génétique)</term><term>Lymphangiogenèse</term><term>Marqueurs biologiques (analyse)</term><term>Mouvement cellulaire</term><term>Mâle</term><term>Oedème (génétique)</term><term>Protéines suppresseurs de tumeurs (génétique)</term><term>Protéines à homéodomaine (génétique)</term><term>Récepteur-3 au facteur croissance endothéliale vasculaire (génétique)</term><term>Régions promotrices (génétique) (génétique)</term><term>Régulation de l'expression des gènes au cours du développement</term><term>Souris</term><term>Souris de lignée C57BL</term><term>Souris de lignée CBA</term><term>Télangiectasie (génétique)</term><term>Vaisseaux lymphatiques (cytologie)</term><term>Vaisseaux lymphatiques (embryologie)</term><term>Vaisseaux lymphatiques (métabolisme)</term><term>Veines (cytologie)</term><term>Éphrine B2 (génétique)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="analysis" xml:lang="en"><term>Biomarkers</term></keywords><keywords scheme="MESH" qualifier="analyse" xml:lang="fr"><term>Marqueurs biologiques</term></keywords><keywords scheme="MESH" qualifier="cytologie" xml:lang="fr"><term>Cellules endothéliales</term><term>Vaisseaux lymphatiques</term><term>Veines</term></keywords><keywords scheme="MESH" qualifier="cytology" xml:lang="en"><term>Endothelial Cells</term><term>Lymphatic Vessels</term><term>Veins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="deficiency" xml:lang="en"><term>SOXF Transcription Factors</term></keywords><keywords scheme="MESH" qualifier="déficit" xml:lang="fr"><term>Facteurs de transcription SOX-F</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>Edema</term><term>Ephrin-B2</term><term>Homeodomain Proteins</term><term>Hypotrichosis</term><term>Promoter Regions, Genetic</term><term>SOXF Transcription Factors</term><term>Telangiectasis</term><term>Tumor Suppressor Proteins</term><term>Vascular Endothelial Growth Factor Receptor-3</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Facteurs de transcription SOX-F</term><term>Hypotrichose</term><term>Oedème</term><term>Protéines suppresseurs de tumeurs</term><term>Protéines à homéodomaine</term><term>Récepteur-3 au facteur croissance endothéliale vasculaire</term><term>Régions promotrices (génétique)</term><term>Télangiectasie</term><term>Éphrine B2</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Endothelial Cells</term><term>Lymphatic Vessels</term><term>SOXF Transcription Factors</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Cellules endothéliales</term><term>Facteurs de transcription SOX-F</term><term>Vaisseaux lymphatiques</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Cell Differentiation</term><term>Cell Movement</term><term>Cells, Cultured</term><term>Female</term><term>Gene Expression Regulation, Developmental</term><term>Lymphangiogenesis</term><term>Male</term><term>Mice</term><term>Mice, Inbred C57BL</term><term>Mice, Inbred CBA</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Cellules cultivées</term><term>Différenciation cellulaire</term><term>Femelle</term><term>Lymphangiogenèse</term><term>Mouvement cellulaire</term><term>Mâle</term><term>Régulation de l'expression des gènes au cours du développement</term><term>Souris</term><term>Souris de lignée C57BL</term><term>Souris de lignée CBA</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The lymphatic system plays a key role in tissue fluid regulation and tumour metastasis, and lymphatic defects underlie many pathological states including lymphoedema, lymphangiectasia, lymphangioma and lymphatic dysplasia. However, the origins of the lymphatic system in the embryo, and the mechanisms that direct growth of the network of lymphatic vessels, remain unclear. Lymphatic vessels are thought to arise from endothelial precursor cells budding from the cardinal vein under the influence of the lymphatic hallmark gene Prox1 (prospero homeobox 1; ref. 4). Defects in the transcription factor gene SOX18 (SRY (sex determining region Y) box 18) cause lymphatic dysfunction in the human syndrome hypotrichosis-lymphoedema-telangiectasia, suggesting that Sox18 may also play a role in lymphatic development or function. Here we use molecular, cellular and genetic assays in mice to show that Sox18 acts as a molecular switch to induce differentiation of lymphatic endothelial cells. Sox18 is expressed in a subset of cardinal vein cells that later co-express Prox1 and migrate to form lymphatic vessels. Sox18 directly activates Prox1 transcription by binding to its proximal promoter. Overexpression of Sox18 in blood vascular endothelial cells induces them to express Prox1 and other lymphatic endothelial markers, while Sox18-null embryos show a complete blockade of lymphatic endothelial cell differentiation from the cardinal vein. Our findings demonstrate a critical role for Sox18 in developmental lymphangiogenesis, and suggest new avenues to investigate for therapeutic management of human lymphangiopathies.</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="Browne, Catherine" sort="Browne, Catherine" uniqKey="Browne C" first="Catherine" last="Browne">Catherine Browne</name><name sortKey="Caprini, Andrea" sort="Caprini, Andrea" uniqKey="Caprini A" first="Andrea" last="Caprini">Andrea Caprini</name><name sortKey="Cheah, Kathryn S E" sort="Cheah, Kathryn S E" uniqKey="Cheah K" first="Kathryn S E" last="Cheah">Kathryn S E. Cheah</name><name sortKey="Davidson, Tara" sort="Davidson, Tara" uniqKey="Davidson T" first="Tara" last="Davidson">Tara Davidson</name><name sortKey="Dejana, Elisabetta" sort="Dejana, Elisabetta" uniqKey="Dejana E" first="Elisabetta" last="Dejana">Elisabetta Dejana</name><name sortKey="Downes, Meredith" sort="Downes, Meredith" uniqKey="Downes M" first="Meredith" last="Downes">Meredith Downes</name><name sortKey="Hosking, Brett" sort="Hosking, Brett" uniqKey="Hosking B" first="Brett" last="Hosking">Brett Hosking</name><name sortKey="Karnezis, Tara" sort="Karnezis, Tara" uniqKey="Karnezis T" first="Tara" last="Karnezis">Tara Karnezis</name><name sortKey="Koopman, Peter" sort="Koopman, Peter" uniqKey="Koopman P" first="Peter" last="Koopman">Peter Koopman</name><name sortKey="Muscat, George E O" sort="Muscat, George E O" uniqKey="Muscat G" first="George E O" last="Muscat">George E O. Muscat</name><name sortKey="Orsenigo, Fabrizio" sort="Orsenigo, Fabrizio" uniqKey="Orsenigo F" first="Fabrizio" last="Orsenigo">Fabrizio Orsenigo</name><name sortKey="Paavonen, Karri" sort="Paavonen, Karri" uniqKey="Paavonen K" first="Karri" last="Paavonen">Karri Paavonen</name><name sortKey="Shayan, Ramin" sort="Shayan, Ramin" uniqKey="Shayan R" first="Ramin" last="Shayan">Ramin Shayan</name><name sortKey="Stacker, Steven A" sort="Stacker, Steven A" uniqKey="Stacker S" first="Steven A" last="Stacker">Steven A. Stacker</name><name sortKey="Tutt, Desmond" sort="Tutt, Desmond" uniqKey="Tutt D" first="Desmond" last="Tutt">Desmond Tutt</name><name sortKey="Wilhelm, Dagmar" sort="Wilhelm, Dagmar" uniqKey="Wilhelm D" first="Dagmar" last="Wilhelm">Dagmar Wilhelm</name></noCountry><country name="Australie"><noRegion><name sortKey="Francois, Mathias" sort="Francois, Mathias" uniqKey="Francois M" first="Mathias" last="François">Mathias François</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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