Fusing VE-Cadherin to α-Catenin Impairs Fetal Liver Hematopoiesis and Lymph but Not Blood Vessel Formation
Identifieur interne : 002A62 ( Main/Exploration ); précédent : 002A61; suivant : 002A63Fusing VE-Cadherin to α-Catenin Impairs Fetal Liver Hematopoiesis and Lymph but Not Blood Vessel Formation
Auteurs : Nina Dartsch ; Dörte Schulte ; René H Gerling ; Friedemann Kiefer ; Dietmar VestweberSource :
- Molecular and Cellular Biology [ 0270-7306 ] ; 2014.
Descripteurs français
- KwdFr :
- Animaux, Antigènes CD (génétique), Antigènes CD (métabolisme), Cadhérines (génétique), Cadhérines (métabolisme), Cellules souches (cytologie), Cellules souches (métabolisme), Cellules souches hématopoïétiques (cytologie), Cellules souches hématopoïétiques (métabolisme), Embryon de mammifère (), Embryon de mammifère (anatomopathologie), Embryon de mammifère (métabolisme), Foie (embryologie), Hématopoïèse, Lymphe (cytologie), Mutation, Néovascularisation physiologique, Oedème (anatomopathologie), Souris, Souris de lignée C57BL, Système lymphatique (embryologie), Vaisseaux sanguins (croissance et développement), alpha-Caténine (génétique), alpha-Caténine (métabolisme).
- MESH :
- anatomopathologie : Embryon de mammifère, Oedème.
- croissance et développement : Vaisseaux sanguins.
- cytologie : Cellules souches, Cellules souches hématopoïétiques, Lymphe.
- embryologie : Foie, Système lymphatique.
- génétique : Antigènes CD, Cadhérines, alpha-Caténine.
- métabolisme : Antigènes CD, Cadhérines, Cellules souches, Cellules souches hématopoïétiques, Embryon de mammifère, alpha-Caténine.
- Animaux, Embryon de mammifère, Hématopoïèse, Mutation, Néovascularisation physiologique, Souris, Souris de lignée C57BL.
English descriptors
- KwdEn :
- Animals, Antigens, CD (genetics), Antigens, CD (metabolism), Blood Vessels (growth & development), Cadherins (genetics), Cadherins (metabolism), Edema (pathology), Embryo, Mammalian (blood supply), Embryo, Mammalian (metabolism), Embryo, Mammalian (pathology), Hematopoiesis, Hematopoietic Stem Cells (cytology), Hematopoietic Stem Cells (metabolism), Liver (embryology), Lymph (cytology), Lymphatic System (embryology), Mice, Mice, Inbred C57BL, Mutation, Neovascularization, Physiologic, Stem Cells (cytology), Stem Cells (metabolism), alpha Catenin (genetics), alpha Catenin (metabolism).
- MESH :
- chemical , genetics : Antigens, CD, Cadherins, alpha Catenin.
- chemical , metabolism : Antigens, CD, Cadherins, alpha Catenin.
- blood supply : Embryo, Mammalian.
- cytology : Hematopoietic Stem Cells, Lymph, Stem Cells.
- embryology : Liver, Lymphatic System.
- growth & development : Blood Vessels.
- metabolism : Embryo, Mammalian, Hematopoietic Stem Cells, Stem Cells.
- pathology : Edema, Embryo, Mammalian.
- Animals, Hematopoiesis, Mice, Mice, Inbred C57BL, Mutation, Neovascularization, Physiologic.
Abstract
We have recently shown that genetic replacement of VE-cadherin by a VE-cadherin–α-catenin fusion construct strongly impairs opening of endothelial cell contacts during leukocyte extravasation and induction of vascular permeability in adult mice. Here we show that this mutation leads to lethality at midgestation on a clean C57BL/6 background. Investigating the reasons for embryonic lethality, we observed a lack of fetal liver hematopoiesis and severe lymphedema but no detectable defects in blood vessel formation and remodeling. As for the hematopoiesis defect, VE-cadherin–α-catenin affected neither the generation of hematopoietic stem and progenitor cells (HSPCs) from hemogenic endothelium nor their differentiation into multiple hematopoietic lineages. Instead, HSPCs accumulated in the fetal circulation, suggesting that their entry into the fetal liver was blocked. Edema formation was caused by disturbed lymphatic vessel development. Lymphatic progenitor cells of VE-cadherin–α-catenin-expressing embryos were able to leave the cardinal vein and migrate to the site of the first lymphatic vessel formation, yet subsequently, these cells failed to form large lumenized lymphatic vessels. Thus, stabilizing endothelial cell contacts by a covalent link between VE-cadherin and α-catenin affects recruitment of hematopoietic progenitors into the fetal liver and the development of lymph but not blood vessels.
Url:
DOI: 10.1128/MCB.01526-13
PubMed: 24567373
PubMed Central: 3993599
Affiliations:
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Le document en format XML
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<term>Antigens, CD (genetics)</term>
<term>Antigens, CD (metabolism)</term>
<term>Blood Vessels (growth & development)</term>
<term>Cadherins (genetics)</term>
<term>Cadherins (metabolism)</term>
<term>Edema (pathology)</term>
<term>Embryo, Mammalian (blood supply)</term>
<term>Embryo, Mammalian (metabolism)</term>
<term>Embryo, Mammalian (pathology)</term>
<term>Hematopoiesis</term>
<term>Hematopoietic Stem Cells (cytology)</term>
<term>Hematopoietic Stem Cells (metabolism)</term>
<term>Liver (embryology)</term>
<term>Lymph (cytology)</term>
<term>Lymphatic System (embryology)</term>
<term>Mice</term>
<term>Mice, Inbred C57BL</term>
<term>Mutation</term>
<term>Neovascularization, Physiologic</term>
<term>Stem Cells (cytology)</term>
<term>Stem Cells (metabolism)</term>
<term>alpha Catenin (genetics)</term>
<term>alpha Catenin (metabolism)</term>
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<term>Antigènes CD (génétique)</term>
<term>Antigènes CD (métabolisme)</term>
<term>Cadhérines (génétique)</term>
<term>Cadhérines (métabolisme)</term>
<term>Cellules souches (cytologie)</term>
<term>Cellules souches (métabolisme)</term>
<term>Cellules souches hématopoïétiques (cytologie)</term>
<term>Cellules souches hématopoïétiques (métabolisme)</term>
<term>Embryon de mammifère ()</term>
<term>Embryon de mammifère (anatomopathologie)</term>
<term>Embryon de mammifère (métabolisme)</term>
<term>Foie (embryologie)</term>
<term>Hématopoïèse</term>
<term>Lymphe (cytologie)</term>
<term>Mutation</term>
<term>Néovascularisation physiologique</term>
<term>Oedème (anatomopathologie)</term>
<term>Souris</term>
<term>Souris de lignée C57BL</term>
<term>Système lymphatique (embryologie)</term>
<term>Vaisseaux sanguins (croissance et développement)</term>
<term>alpha-Caténine (génétique)</term>
<term>alpha-Caténine (métabolisme)</term>
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<term>alpha Catenin</term>
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<term>Cellules souches hématopoïétiques</term>
<term>Lymphe</term>
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<term>Stem Cells</term>
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<term>Système lymphatique</term>
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<keywords scheme="MESH" qualifier="embryology" xml:lang="en"><term>Liver</term>
<term>Lymphatic System</term>
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<term>Cellules souches hématopoïétiques</term>
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<front><div type="abstract" xml:lang="en"><p>We have recently shown that genetic replacement of VE-cadherin by a VE-cadherin–α-catenin fusion construct strongly impairs opening of endothelial cell contacts during leukocyte extravasation and induction of vascular permeability in adult mice. Here we show that this mutation leads to lethality at midgestation on a clean C57BL/6 background. Investigating the reasons for embryonic lethality, we observed a lack of fetal liver hematopoiesis and severe lymphedema but no detectable defects in blood vessel formation and remodeling. As for the hematopoiesis defect, VE-cadherin–α-catenin affected neither the generation of hematopoietic stem and progenitor cells (HSPCs) from hemogenic endothelium nor their differentiation into multiple hematopoietic lineages. Instead, HSPCs accumulated in the fetal circulation, suggesting that their entry into the fetal liver was blocked. Edema formation was caused by disturbed lymphatic vessel development. Lymphatic progenitor cells of VE-cadherin–α-catenin-expressing embryos were able to leave the cardinal vein and migrate to the site of the first lymphatic vessel formation, yet subsequently, these cells failed to form large lumenized lymphatic vessels. Thus, stabilizing endothelial cell contacts by a covalent link between VE-cadherin and α-catenin affects recruitment of hematopoietic progenitors into the fetal liver and the development of lymph but not blood vessels.</p>
</div>
</front>
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<affiliations><list></list>
<tree><noCountry><name sortKey="Dartsch, Nina" sort="Dartsch, Nina" uniqKey="Dartsch N" first="Nina" last="Dartsch">Nina Dartsch</name>
<name sortKey="H Gerling, Rene" sort="H Gerling, Rene" uniqKey="H Gerling R" first="René" last="H Gerling">René H Gerling</name>
<name sortKey="Kiefer, Friedemann" sort="Kiefer, Friedemann" uniqKey="Kiefer F" first="Friedemann" last="Kiefer">Friedemann Kiefer</name>
<name sortKey="Schulte, Dorte" sort="Schulte, Dorte" uniqKey="Schulte D" first="Dörte" last="Schulte">Dörte Schulte</name>
<name sortKey="Vestweber, Dietmar" sort="Vestweber, Dietmar" uniqKey="Vestweber D" first="Dietmar" last="Vestweber">Dietmar Vestweber</name>
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