Connexin37 and Connexin43 deficiencies in mice disrupt lymphatic valve development and result in lymphatic disorders including lymphedema and chylothorax
Identifieur interne : 004298 ( Ncbi/Merge ); précédent : 004297; suivant : 004299Connexin37 and Connexin43 deficiencies in mice disrupt lymphatic valve development and result in lymphatic disorders including lymphedema and chylothorax
Auteurs : John D. Kanady [États-Unis] ; Michael T. Dellinger [États-Unis] ; Stephanie J. Munger [États-Unis] ; Marlys H. Witte [États-Unis] ; Alexander M. Simon [États-Unis]Source :
- Developmental biology [ 0012-1606 ] ; 2011.
Descripteurs français
- KwdFr :
- Animaux, Chylothorax (anatomopathologie), Chylothorax (génétique), Chylothorax (physiopathologie), Connexine 43 (génétique), Connexine 43 (métabolisme), Connexines (génétique), Connexines (métabolisme), Facteurs de transcription Forkhead (métabolisme), Lymphangiogenèse, Lymphoedème (anatomopathologie), Lymphoedème (génétique), Lymphoedème (physiopathologie), Souris, Souris knockout, Vaisseaux lymphatiques (malformations), Vaisseaux lymphatiques (métabolisme).
- MESH :
- anatomopathologie : Chylothorax, Lymphoedème.
- génétique : Chylothorax, Connexine 43, Connexines, Lymphoedème.
- malformations : Vaisseaux lymphatiques.
- métabolisme : Connexine 43, Connexines, Facteurs de transcription Forkhead, Vaisseaux lymphatiques.
- physiopathologie : Chylothorax, Lymphoedème.
- Animaux, Lymphangiogenèse, Souris, Souris knockout.
English descriptors
- KwdEn :
- Animals, Chylothorax (genetics), Chylothorax (pathology), Chylothorax (physiopathology), Connexin 43 (genetics), Connexin 43 (metabolism), Connexins (genetics), Connexins (metabolism), Forkhead Transcription Factors (metabolism), Lymphangiogenesis, Lymphatic Vessels (abnormalities), Lymphatic Vessels (metabolism), Lymphedema (genetics), Lymphedema (pathology), Lymphedema (physiopathology), Mice, Mice, Knockout.
- MESH :
- chemical , genetics : Connexin 43, Connexins.
- abnormalities : Lymphatic Vessels.
- genetics : Chylothorax, Lymphedema.
- chemical , metabolism : Connexin 43, Connexins, Forkhead Transcription Factors, Lymphatic Vessels.
- pathology : Chylothorax, Lymphedema.
- physiopathology : Chylothorax, Lymphedema.
- Animals, Lymphangiogenesis, Mice, Mice, Knockout.
Abstract
Intraluminal valves are required for the proper function of lymphatic collecting vessels and large lymphatic trunks like the thoracic duct. Despite recent progress in the study of lymphvasculogenesis and lymphangiogenesis, the molecular mechanisms controlling the morphogenesis of lymphatic valves remains poorly understood. Here, we report that gap junction proteins, or connexins (Cxs), are required for lymphatic valvulogenesis. Cx37 and Cx43 are expressed early in mouse lymphatic development in the jugular lymph sacs, and later in development these Cxs become enriched and differentially expressed by lymphatic endothelial cells on the upstream and downstream sides of the valves. Specific deficiencies of Cx37 and Cx43 alone or in combination result in defective valve formation in lymphatic collecting vessels, lymphedema, and chylothorax. We also show that Cx37 regulates jugular lymph sac size and that both Cx37 and Cx43 are required for normal thoracic duct development, including valve formation. Another Cx family member, Cx47, whose human analog is mutated in some families with lymphedema, is also highly enriched in a subset of endothelial cells in lymphatic valves. Mechanistically, we present data from Foxc2−/− embryos suggesting that Cx37 may be a target of regulation by Foxc2, a transcription factor that is mutated in human lymphedema-distichiasis syndrome. These results show that at least three Cxs are expressed in the developing lymphatic vasculature and, when defective, are associated with clinically manifest lymphatic disorders in mice and man.
Url:
DOI: 10.1016/j.ydbio.2011.04.004
PubMed: 21515254
PubMed Central: 3134316
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PMC:3134316Le document en format XML
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Despite recent progress in the study of lymphvasculogenesis and lymphangiogenesis, the molecular mechanisms controlling the morphogenesis of lymphatic valves remains poorly understood. Here, we report that gap junction proteins, or connexins (Cxs), are required for lymphatic valvulogenesis. Cx37 and Cx43 are expressed early in mouse lymphatic development in the jugular lymph sacs, and later in development these Cxs become enriched and differentially expressed by lymphatic endothelial cells on the upstream and downstream sides of the valves. Specific deficiencies of Cx37 and Cx43 alone or in combination result in defective valve formation in lymphatic collecting vessels, lymphedema, and chylothorax. We also show that Cx37 regulates jugular lymph sac size and that both Cx37 and Cx43 are required for normal thoracic duct development, including valve formation. Another Cx family member, Cx47, whose human analog is mutated in some families with lymphedema, is also highly enriched in a subset of endothelial cells in lymphatic valves. Mechanistically, we present data from Foxc2−/− embryos suggesting that Cx37 may be a target of regulation by Foxc2, a transcription factor that is mutated in human lymphedema-distichiasis syndrome. These results show that at least three Cxs are expressed in the developing lymphatic vasculature and, when defective, are associated with clinically manifest lymphatic disorders in mice and man.</p></div></front></TEI><double pmid="21515254"><pmc><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Connexin37 and Connexin43 deficiencies in mice disrupt lymphatic valve development and result in lymphatic disorders including lymphedema and chylothorax</title><author><name sortKey="Kanady, John D" sort="Kanady, John D" uniqKey="Kanady J" first="John D." last="Kanady">John D. Kanady</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Physiology, University of Arizona, Tucson, AZ 85724, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Physiology, University of Arizona, Tucson, AZ 85724</wicri:regionArea><wicri:noRegion>AZ 85724</wicri:noRegion></affiliation></author><author><name sortKey="Dellinger, Michael T" sort="Dellinger, Michael T" uniqKey="Dellinger M" first="Michael T." last="Dellinger">Michael T. Dellinger</name><affiliation wicri:level="1"><nlm:aff id="A2">Department of Molecular and Cellular Biology, University of Arizona, Tucson, AZ 85724, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Molecular and Cellular Biology, University of Arizona, Tucson, AZ 85724</wicri:regionArea><wicri:noRegion>AZ 85724</wicri:noRegion></affiliation></author><author><name sortKey="Munger, Stephanie J" sort="Munger, Stephanie J" uniqKey="Munger S" first="Stephanie J." last="Munger">Stephanie J. Munger</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Physiology, University of Arizona, Tucson, AZ 85724, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Physiology, University of Arizona, Tucson, AZ 85724</wicri:regionArea><wicri:noRegion>AZ 85724</wicri:noRegion></affiliation></author><author><name sortKey="Witte, Marlys H" sort="Witte, Marlys H" uniqKey="Witte M" first="Marlys H." last="Witte">Marlys H. Witte</name><affiliation wicri:level="1"><nlm:aff id="A3">Department of Surgery, University of Arizona, Tucson, AZ 85724, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Surgery, University of Arizona, Tucson, AZ 85724</wicri:regionArea><wicri:noRegion>AZ 85724</wicri:noRegion></affiliation></author><author><name sortKey="Simon, Alexander M" sort="Simon, Alexander M" uniqKey="Simon A" first="Alexander M." last="Simon">Alexander M. Simon</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Physiology, University of Arizona, Tucson, AZ 85724, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Physiology, University of Arizona, Tucson, AZ 85724</wicri:regionArea><wicri:noRegion>AZ 85724</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">21515254</idno><idno type="pmc">3134316</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3134316</idno><idno type="RBID">PMC:3134316</idno><idno type="doi">10.1016/j.ydbio.2011.04.004</idno><date when="2011">2011</date><idno type="wicri:Area/Pmc/Corpus">002974</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">002974</idno><idno type="wicri:Area/Pmc/Curation">002973</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">002973</idno><idno type="wicri:Area/Pmc/Checkpoint">003030</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">003030</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Connexin37 and Connexin43 deficiencies in mice disrupt lymphatic valve development and result in lymphatic disorders including lymphedema and chylothorax</title><author><name sortKey="Kanady, John D" sort="Kanady, John D" uniqKey="Kanady J" first="John D." last="Kanady">John D. Kanady</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Physiology, University of Arizona, Tucson, AZ 85724, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Physiology, University of Arizona, Tucson, AZ 85724</wicri:regionArea><wicri:noRegion>AZ 85724</wicri:noRegion></affiliation></author><author><name sortKey="Dellinger, Michael T" sort="Dellinger, Michael T" uniqKey="Dellinger M" first="Michael T." last="Dellinger">Michael T. Dellinger</name><affiliation wicri:level="1"><nlm:aff id="A2">Department of Molecular and Cellular Biology, University of Arizona, Tucson, AZ 85724, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Molecular and Cellular Biology, University of Arizona, Tucson, AZ 85724</wicri:regionArea><wicri:noRegion>AZ 85724</wicri:noRegion></affiliation></author><author><name sortKey="Munger, Stephanie J" sort="Munger, Stephanie J" uniqKey="Munger S" first="Stephanie J." last="Munger">Stephanie J. Munger</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Physiology, University of Arizona, Tucson, AZ 85724, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Physiology, University of Arizona, Tucson, AZ 85724</wicri:regionArea><wicri:noRegion>AZ 85724</wicri:noRegion></affiliation></author><author><name sortKey="Witte, Marlys H" sort="Witte, Marlys H" uniqKey="Witte M" first="Marlys H." last="Witte">Marlys H. Witte</name><affiliation wicri:level="1"><nlm:aff id="A3">Department of Surgery, University of Arizona, Tucson, AZ 85724, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Surgery, University of Arizona, Tucson, AZ 85724</wicri:regionArea><wicri:noRegion>AZ 85724</wicri:noRegion></affiliation></author><author><name sortKey="Simon, Alexander M" sort="Simon, Alexander M" uniqKey="Simon A" first="Alexander M." last="Simon">Alexander M. Simon</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Physiology, University of Arizona, Tucson, AZ 85724, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Physiology, University of Arizona, Tucson, AZ 85724</wicri:regionArea><wicri:noRegion>AZ 85724</wicri:noRegion></affiliation></author></analytic><series><title level="j">Developmental biology</title><idno type="ISSN">0012-1606</idno><idno type="eISSN">1095-564X</idno><imprint><date when="2011">2011</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="P2">Intraluminal valves are required for the proper function of lymphatic collecting vessels and large lymphatic trunks like the thoracic duct. Despite recent progress in the study of lymphvasculogenesis and lymphangiogenesis, the molecular mechanisms controlling the morphogenesis of lymphatic valves remains poorly understood. Here, we report that gap junction proteins, or connexins (Cxs), are required for lymphatic valvulogenesis. Cx37 and Cx43 are expressed early in mouse lymphatic development in the jugular lymph sacs, and later in development these Cxs become enriched and differentially expressed by lymphatic endothelial cells on the upstream and downstream sides of the valves. Specific deficiencies of Cx37 and Cx43 alone or in combination result in defective valve formation in lymphatic collecting vessels, lymphedema, and chylothorax. We also show that Cx37 regulates jugular lymph sac size and that both Cx37 and Cx43 are required for normal thoracic duct development, including valve formation. Another Cx family member, Cx47, whose human analog is mutated in some families with lymphedema, is also highly enriched in a subset of endothelial cells in lymphatic valves. Mechanistically, we present data from Foxc2−/− embryos suggesting that Cx37 may be a target of regulation by Foxc2, a transcription factor that is mutated in human lymphedema-distichiasis syndrome. These results show that at least three Cxs are expressed in the developing lymphatic vasculature and, when defective, are associated with clinically manifest lymphatic disorders in mice and man.</p></div></front></TEI></pmc><pubmed><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Connexin37 and Connexin43 deficiencies in mice disrupt lymphatic valve development and result in lymphatic disorders including lymphedema and chylothorax.</title><author><name sortKey="Kanady, John D" sort="Kanady, John D" uniqKey="Kanady J" first="John D" last="Kanady">John D. Kanady</name><affiliation wicri:level="2"><nlm:affiliation>Department of Physiology, University of Arizona, Tucson, AZ 85724, USA. jkanady@email.arizona.edu</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Physiology, University of Arizona, Tucson, AZ 85724</wicri:regionArea><placeName><region type="state">Arizona</region></placeName></affiliation></author><author><name sortKey="Dellinger, Michael T" sort="Dellinger, Michael T" uniqKey="Dellinger M" first="Michael T" last="Dellinger">Michael T. Dellinger</name></author><author><name sortKey="Munger, Stephanie J" sort="Munger, Stephanie J" uniqKey="Munger S" first="Stephanie J" last="Munger">Stephanie J. Munger</name></author><author><name sortKey="Witte, Marlys H" sort="Witte, Marlys H" uniqKey="Witte M" first="Marlys H" last="Witte">Marlys H. Witte</name></author><author><name sortKey="Simon, Alexander M" sort="Simon, Alexander M" uniqKey="Simon A" first="Alexander M" last="Simon">Alexander M. Simon</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2011">2011</date><idno type="RBID">pubmed:21515254</idno><idno type="pmid">21515254</idno><idno type="doi">10.1016/j.ydbio.2011.04.004</idno><idno type="wicri:Area/PubMed/Corpus">002656</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">002656</idno><idno type="wicri:Area/PubMed/Curation">002656</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">002656</idno><idno type="wicri:Area/PubMed/Checkpoint">002656</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">002656</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Connexin37 and Connexin43 deficiencies in mice disrupt lymphatic valve development and result in lymphatic disorders including lymphedema and chylothorax.</title><author><name sortKey="Kanady, John D" sort="Kanady, John D" uniqKey="Kanady J" first="John D" last="Kanady">John D. Kanady</name><affiliation wicri:level="2"><nlm:affiliation>Department of Physiology, University of Arizona, Tucson, AZ 85724, USA. jkanady@email.arizona.edu</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Physiology, University of Arizona, Tucson, AZ 85724</wicri:regionArea><placeName><region type="state">Arizona</region></placeName></affiliation></author><author><name sortKey="Dellinger, Michael T" sort="Dellinger, Michael T" uniqKey="Dellinger M" first="Michael T" last="Dellinger">Michael T. Dellinger</name></author><author><name sortKey="Munger, Stephanie J" sort="Munger, Stephanie J" uniqKey="Munger S" first="Stephanie J" last="Munger">Stephanie J. Munger</name></author><author><name sortKey="Witte, Marlys H" sort="Witte, Marlys H" uniqKey="Witte M" first="Marlys H" last="Witte">Marlys H. Witte</name></author><author><name sortKey="Simon, Alexander M" sort="Simon, Alexander M" uniqKey="Simon A" first="Alexander M" last="Simon">Alexander M. Simon</name></author></analytic><series><title level="j">Developmental biology</title><idno type="eISSN">1095-564X</idno><imprint><date when="2011" type="published">2011</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Chylothorax (genetics)</term><term>Chylothorax (pathology)</term><term>Chylothorax (physiopathology)</term><term>Connexin 43 (genetics)</term><term>Connexin 43 (metabolism)</term><term>Connexins (genetics)</term><term>Connexins (metabolism)</term><term>Forkhead Transcription Factors (metabolism)</term><term>Lymphangiogenesis</term><term>Lymphatic Vessels (abnormalities)</term><term>Lymphatic Vessels (metabolism)</term><term>Lymphedema (genetics)</term><term>Lymphedema (pathology)</term><term>Lymphedema (physiopathology)</term><term>Mice</term><term>Mice, Knockout</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Chylothorax (anatomopathologie)</term><term>Chylothorax (génétique)</term><term>Chylothorax (physiopathologie)</term><term>Connexine 43 (génétique)</term><term>Connexine 43 (métabolisme)</term><term>Connexines (génétique)</term><term>Connexines (métabolisme)</term><term>Facteurs de transcription Forkhead (métabolisme)</term><term>Lymphangiogenèse</term><term>Lymphoedème (anatomopathologie)</term><term>Lymphoedème (génétique)</term><term>Lymphoedème (physiopathologie)</term><term>Souris</term><term>Souris knockout</term><term>Vaisseaux lymphatiques (malformations)</term><term>Vaisseaux lymphatiques (métabolisme)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Connexin 43</term><term>Connexins</term></keywords><keywords scheme="MESH" qualifier="abnormalities" xml:lang="en"><term>Lymphatic Vessels</term></keywords><keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Chylothorax</term><term>Lymphoedème</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Chylothorax</term><term>Lymphedema</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Chylothorax</term><term>Connexine 43</term><term>Connexines</term><term>Lymphoedème</term></keywords><keywords scheme="MESH" qualifier="malformations" xml:lang="fr"><term>Vaisseaux lymphatiques</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Connexin 43</term><term>Connexins</term><term>Forkhead Transcription Factors</term><term>Lymphatic Vessels</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Connexine 43</term><term>Connexines</term><term>Facteurs de transcription Forkhead</term><term>Vaisseaux lymphatiques</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Chylothorax</term><term>Lymphedema</term></keywords><keywords scheme="MESH" qualifier="physiopathologie" xml:lang="fr"><term>Chylothorax</term><term>Lymphoedème</term></keywords><keywords scheme="MESH" qualifier="physiopathology" xml:lang="en"><term>Chylothorax</term><term>Lymphedema</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Lymphangiogenesis</term><term>Mice</term><term>Mice, Knockout</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Lymphangiogenèse</term><term>Souris</term><term>Souris knockout</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Intraluminal valves are required for the proper function of lymphatic collecting vessels and large lymphatic trunks like the thoracic duct. Despite recent progress in the study of lymphvasculogenesis and lymphangiogenesis, the molecular mechanisms controlling the morphogenesis of lymphatic valves remain poorly understood. Here, we report that gap junction proteins, or connexins (Cxs), are required for lymphatic valvulogenesis. Cx37 and Cx43 are expressed early in mouse lymphatic development in the jugular lymph sacs, and later in development these Cxs become enriched and differentially expressed by lymphatic endothelial cells on the upstream and downstream sides of the valves. Specific deficiencies of Cx37 and Cx43 alone or in combination result in defective valve formation in lymphatic collecting vessels, lymphedema, and chylothorax. We also show that Cx37 regulates jugular lymph sac size and that both Cx37 and Cx43 are required for normal thoracic duct development, including valve formation. Another Cx family member, Cx47, whose human analog is mutated in some families with lymphedema, is also highly enriched in a subset of endothelial cells in lymphatic valves. Mechanistically, we present data from Foxc2-/- embryos suggesting that Cx37 may be a target of regulation by Foxc2, a transcription factor that is mutated in human lymphedema-distichiasis syndrome. These results show that at least three Cxs are expressed in the developing lymphatic vasculature and, when defective, are associated with clinically manifest lymphatic disorders in mice and man.</div></front></TEI></pubmed></double></record>Pour manipuler ce document sous Unix (Dilib)
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