FOXC2 controls formation and maturation of lymphatic collecting vessels through cooperation with NFATc1
Identifieur interne : 006287 ( Main/Exploration ); précédent : 006286; suivant : 006288FOXC2 controls formation and maturation of lymphatic collecting vessels through cooperation with NFATc1
Auteurs : Camilla Norrmén ; Konstantin I. Ivanov ; Jianpin Cheng ; Nadine Zangger ; Mauro Delorenzi ; Muriel Jaquet ; Naoyuki Miura ; Pauli Puolakkainen ; Valerie Horsley ; Junhao Hu ; Hellmut G. Augustin ; Seppo Yl Herttuala ; Kari Alitalo [Finlande] ; Tatiana V. PetrovaSource :
- The Journal of Cell Biology [ 0021-9525 ] ; 2009.
Abstract
The mechanisms of blood vessel maturation into distinct parts of the blood vasculature such as arteries, veins, and capillaries have been the subject of intense investigation over recent years. In contrast, our knowledge of lymphatic vessel maturation is still fragmentary. In this study, we provide a molecular and morphological characterization of the major steps in the maturation of the primary lymphatic capillary plexus into collecting lymphatic vessels during development and show that forkhead transcription factor Foxc2 controls this process. We further identify transcription factor NFATc1 as a novel regulator of lymphatic development and describe a previously unsuspected link between NFATc1 and Foxc2 in the regulation of lymphatic maturation. We also provide a genome-wide map of FOXC2-binding sites in lymphatic endothelial cells, identify a novel consensus FOXC2 sequence, and show that NFATc1 physically interacts with FOXC2-binding enhancers. As damage to collecting vessels is a major cause of lymphatic dysfunction in humans, our results suggest that FOXC2 and NFATc1 are potential targets for therapeutic intervention.
Url:
DOI: 10.1083/jcb.200901104
PubMed: 19398761
PubMed Central: 2700385
Affiliations:
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Ivanov</name><affiliation><nlm:aff id="aff1"><institution>Molecular Cancer Biology Program, Biomedicum Helsinki</institution>,</nlm:aff></affiliation></author><author><name sortKey="Cheng, Jianpin" sort="Cheng, Jianpin" uniqKey="Cheng J" first="Jianpin" last="Cheng">Jianpin Cheng</name><affiliation><nlm:aff id="aff1"><institution>Molecular Cancer Biology Program, Biomedicum Helsinki</institution>,</nlm:aff></affiliation></author><author><name sortKey="Zangger, Nadine" sort="Zangger, Nadine" uniqKey="Zangger N" first="Nadine" last="Zangger">Nadine Zangger</name><affiliation><nlm:aff id="aff2"><institution>Swiss Institute of Bioinformatics, Génopode, 1015 Lausanne, Switzerland</institution></nlm:aff></affiliation></author><author><name sortKey="Delorenzi, Mauro" sort="Delorenzi, Mauro" uniqKey="Delorenzi M" first="Mauro" last="Delorenzi">Mauro Delorenzi</name><affiliation><nlm:aff id="aff2"><institution>Swiss Institute of Bioinformatics, Génopode, 1015 Lausanne, Switzerland</institution></nlm:aff></affiliation></author><author><name sortKey="Jaquet, Muriel" sort="Jaquet, Muriel" uniqKey="Jaquet M" first="Muriel" last="Jaquet">Muriel Jaquet</name><affiliation><nlm:aff id="aff3"><institution>Division of Experimental Oncology, Multidisciplinary Oncology Center, University of Lausanne, 1066 Epalinges, Switzerland</institution></nlm:aff></affiliation></author><author><name sortKey="Miura, Naoyuki" sort="Miura, Naoyuki" uniqKey="Miura N" first="Naoyuki" last="Miura">Naoyuki Miura</name><affiliation><nlm:aff id="aff4"><institution>Department of Biochemistry, Hamamatsu University School of Medicine, 431-3192 Hamamatsu, Japan</institution></nlm:aff></affiliation></author><author><name sortKey="Puolakkainen, Pauli" sort="Puolakkainen, Pauli" uniqKey="Puolakkainen P" first="Pauli" last="Puolakkainen">Pauli Puolakkainen</name><affiliation><nlm:aff wicri:cut=", and" id="aff1"><institution>Department of Surgery, Helsinki University Central Hospital</institution></nlm:aff></affiliation></author><author><name sortKey="Horsley, Valerie" sort="Horsley, Valerie" uniqKey="Horsley V" first="Valerie" last="Horsley">Valerie Horsley</name><affiliation><nlm:aff id="aff5"><institution>Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065</institution></nlm:aff></affiliation></author><author><name sortKey="Hu, Junhao" sort="Hu, Junhao" uniqKey="Hu J" first="Junhao" last="Hu">Junhao Hu</name><affiliation><nlm:aff id="aff6"><institution>Joint Research Division of Vascular Biology, Centre for Biomedicine and Medical Technology Mannheim, Heidelberg University and German Cancer Research Center (DKFZ-ZMBH Alliance), 69120 Heidelberg, Germany</institution></nlm:aff></affiliation></author><author><name sortKey="Augustin, Hellmut G" sort="Augustin, Hellmut G" uniqKey="Augustin H" first="Hellmut G." last="Augustin">Hellmut G. 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Ivanov</name><affiliation><nlm:aff id="aff1"><institution>Molecular Cancer Biology Program, Biomedicum Helsinki</institution>,</nlm:aff></affiliation></author><author><name sortKey="Cheng, Jianpin" sort="Cheng, Jianpin" uniqKey="Cheng J" first="Jianpin" last="Cheng">Jianpin Cheng</name><affiliation><nlm:aff id="aff1"><institution>Molecular Cancer Biology Program, Biomedicum Helsinki</institution>,</nlm:aff></affiliation></author><author><name sortKey="Zangger, Nadine" sort="Zangger, Nadine" uniqKey="Zangger N" first="Nadine" last="Zangger">Nadine Zangger</name><affiliation><nlm:aff id="aff2"><institution>Swiss Institute of Bioinformatics, Génopode, 1015 Lausanne, Switzerland</institution></nlm:aff></affiliation></author><author><name sortKey="Delorenzi, Mauro" sort="Delorenzi, Mauro" uniqKey="Delorenzi M" first="Mauro" last="Delorenzi">Mauro Delorenzi</name><affiliation><nlm:aff id="aff2"><institution>Swiss Institute of Bioinformatics, Génopode, 1015 Lausanne, Switzerland</institution></nlm:aff></affiliation></author><author><name sortKey="Jaquet, Muriel" sort="Jaquet, Muriel" uniqKey="Jaquet M" first="Muriel" last="Jaquet">Muriel Jaquet</name><affiliation><nlm:aff id="aff3"><institution>Division of Experimental Oncology, Multidisciplinary Oncology Center, University of Lausanne, 1066 Epalinges, Switzerland</institution></nlm:aff></affiliation></author><author><name sortKey="Miura, Naoyuki" sort="Miura, Naoyuki" uniqKey="Miura N" first="Naoyuki" last="Miura">Naoyuki Miura</name><affiliation><nlm:aff id="aff4"><institution>Department of Biochemistry, Hamamatsu University School of Medicine, 431-3192 Hamamatsu, Japan</institution></nlm:aff></affiliation></author><author><name sortKey="Puolakkainen, Pauli" sort="Puolakkainen, Pauli" uniqKey="Puolakkainen P" first="Pauli" last="Puolakkainen">Pauli Puolakkainen</name><affiliation><nlm:aff wicri:cut=", and" id="aff1"><institution>Department of Surgery, Helsinki University Central Hospital</institution></nlm:aff></affiliation></author><author><name sortKey="Horsley, Valerie" sort="Horsley, Valerie" uniqKey="Horsley V" first="Valerie" last="Horsley">Valerie Horsley</name><affiliation><nlm:aff id="aff5"><institution>Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065</institution></nlm:aff></affiliation></author><author><name sortKey="Hu, Junhao" sort="Hu, Junhao" uniqKey="Hu J" first="Junhao" last="Hu">Junhao Hu</name><affiliation><nlm:aff id="aff6"><institution>Joint Research Division of Vascular Biology, Centre for Biomedicine and Medical Technology Mannheim, Heidelberg University and German Cancer Research Center (DKFZ-ZMBH Alliance), 69120 Heidelberg, Germany</institution></nlm:aff></affiliation></author><author><name sortKey="Augustin, Hellmut G" sort="Augustin, Hellmut G" uniqKey="Augustin H" first="Hellmut G." last="Augustin">Hellmut G. Augustin</name><affiliation><nlm:aff id="aff6"><institution>Joint Research Division of Vascular Biology, Centre for Biomedicine and Medical Technology Mannheim, Heidelberg University and German Cancer Research Center (DKFZ-ZMBH Alliance), 69120 Heidelberg, Germany</institution></nlm:aff></affiliation></author><author><name sortKey="Yl Herttuala, Seppo" sort="Yl Herttuala, Seppo" uniqKey="Yl Herttuala S" first="Seppo" last="Yl Herttuala">Seppo Yl Herttuala</name><affiliation><nlm:aff id="aff7"><institution>A.I. Virtanen Institute, University of Kuopio, 70211 Kuopio, Finland</institution></nlm:aff></affiliation></author><author><name sortKey="Alitalo, Kari" sort="Alitalo, Kari" uniqKey="Alitalo K" first="Kari" last="Alitalo">Kari Alitalo</name><affiliation><nlm:aff id="aff1"><institution>Molecular Cancer Biology Program, Biomedicum Helsinki</institution>,</nlm:aff><country>Finlande</country><placeName><settlement type="city">Helsinki</settlement><region type="région" nuts="2">Uusimaa</region></placeName><orgName type="university">Université d'Helsinki</orgName></affiliation><affiliation><nlm:aff id="aff1"><institution>Department of Pathology, Haartman Institute and Helsinki University Central Hospital, University of Helsinki, 00014 Helsinki, Finland</institution></nlm:aff><country>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><author><name sortKey="Petrova, Tatiana V" sort="Petrova, Tatiana V" uniqKey="Petrova T" first="Tatiana V." last="Petrova">Tatiana V. Petrova</name><affiliation><nlm:aff id="aff1"><institution>Molecular Cancer Biology Program, Biomedicum Helsinki</institution>,</nlm:aff></affiliation><affiliation><nlm:aff id="aff3"><institution>Division of Experimental Oncology, Multidisciplinary Oncology Center, University of Lausanne, 1066 Epalinges, Switzerland</institution></nlm:aff></affiliation></author></analytic><series><title level="j">The Journal of Cell Biology</title><idno type="ISSN">0021-9525</idno><idno type="eISSN">1540-8140</idno><imprint><date when="2009">2009</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>The mechanisms of blood vessel maturation into distinct parts of the blood vasculature such as arteries, veins, and capillaries have been the subject of intense investigation over recent years. In contrast, our knowledge of lymphatic vessel maturation is still fragmentary. In this study, we provide a molecular and morphological characterization of the major steps in the maturation of the primary lymphatic capillary plexus into collecting lymphatic vessels during development and show that forkhead transcription factor Foxc2 controls this process. We further identify transcription factor NFATc1 as a novel regulator of lymphatic development and describe a previously unsuspected link between NFATc1 and Foxc2 in the regulation of lymphatic maturation. We also provide a genome-wide map of FOXC2-binding sites in lymphatic endothelial cells, identify a novel consensus FOXC2 sequence, and show that NFATc1 physically interacts with FOXC2-binding enhancers. As damage to collecting vessels is a major cause of lymphatic dysfunction in humans, our results suggest that FOXC2 and NFATc1 are potential targets for therapeutic intervention.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Armstrong, E J" uniqKey="Armstrong E">E.J. Armstrong</name></author><author><name sortKey="Bischoff, J" uniqKey="Bischoff J">J. Bischoff</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bailey, T L" uniqKey="Bailey T">T.L. Bailey</name></author><author><name sortKey="Elkan, C" uniqKey="Elkan C">C. Elkan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bettelli, E" uniqKey="Bettelli E">E. Bettelli</name></author><author><name sortKey="Dastrange, M" uniqKey="Dastrange M">M. Dastrange</name></author><author><name sortKey="Oukka, M" uniqKey="Oukka M">M. 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Miura</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Finlande</li></country><region><li>Uusimaa</li></region><settlement><li>Helsinki</li></settlement><orgName><li>Université d'Helsinki</li></orgName></list><tree><noCountry><name sortKey="Augustin, Hellmut G" sort="Augustin, Hellmut G" uniqKey="Augustin H" first="Hellmut G." last="Augustin">Hellmut G. Augustin</name><name sortKey="Cheng, Jianpin" sort="Cheng, Jianpin" uniqKey="Cheng J" first="Jianpin" last="Cheng">Jianpin Cheng</name><name sortKey="Delorenzi, Mauro" sort="Delorenzi, Mauro" uniqKey="Delorenzi M" first="Mauro" last="Delorenzi">Mauro Delorenzi</name><name sortKey="Horsley, Valerie" sort="Horsley, Valerie" uniqKey="Horsley V" first="Valerie" last="Horsley">Valerie Horsley</name><name sortKey="Hu, Junhao" sort="Hu, Junhao" uniqKey="Hu J" first="Junhao" last="Hu">Junhao Hu</name><name sortKey="Ivanov, Konstantin I" sort="Ivanov, Konstantin I" uniqKey="Ivanov K" first="Konstantin I." last="Ivanov">Konstantin I. Ivanov</name><name sortKey="Jaquet, Muriel" sort="Jaquet, Muriel" uniqKey="Jaquet M" first="Muriel" last="Jaquet">Muriel Jaquet</name><name sortKey="Miura, Naoyuki" sort="Miura, Naoyuki" uniqKey="Miura N" first="Naoyuki" last="Miura">Naoyuki Miura</name><name sortKey="Norrmen, Camilla" sort="Norrmen, Camilla" uniqKey="Norrmen C" first="Camilla" last="Norrmén">Camilla Norrmén</name><name sortKey="Petrova, Tatiana V" sort="Petrova, Tatiana V" uniqKey="Petrova T" first="Tatiana V." last="Petrova">Tatiana V. Petrova</name><name sortKey="Puolakkainen, Pauli" sort="Puolakkainen, Pauli" uniqKey="Puolakkainen P" first="Pauli" last="Puolakkainen">Pauli Puolakkainen</name><name sortKey="Yl Herttuala, Seppo" sort="Yl Herttuala, Seppo" uniqKey="Yl Herttuala S" first="Seppo" last="Yl Herttuala">Seppo Yl Herttuala</name><name sortKey="Zangger, Nadine" sort="Zangger, Nadine" uniqKey="Zangger N" first="Nadine" last="Zangger">Nadine Zangger</name></noCountry><country name="Finlande"><region name="Uusimaa"><name sortKey="Alitalo, Kari" sort="Alitalo, Kari" uniqKey="Alitalo K" first="Kari" last="Alitalo">Kari Alitalo</name></region><name sortKey="Alitalo, Kari" sort="Alitalo, Kari" uniqKey="Alitalo K" first="Kari" last="Alitalo">Kari Alitalo</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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