LymphedemaV1, Main, Exploration, bibRecord, 002037

Cdk5 controls lymphatic vessel development and function by phosphorylation of Foxc2.

Identifieur interne : 002037 ( Main/Exploration ); précédent : 002036; suivant : 002038

Cdk5 controls lymphatic vessel development and function by phosphorylation of Foxc2.

Auteurs : Johanna Liebl [Allemagne] ; Siwei Zhang [Allemagne] ; Markus Moser [Allemagne] ; Yan Agalarov [Suisse] ; Cansaran Saygili Demir [Suisse] ; Bianca Hager [Allemagne] ; James A. Bibb [États-Unis] ; Ralf H. Adams [Allemagne] ; Friedemann Kiefer [Allemagne] ; Naoyuki Miura [Japon] ; Tatiana V. Petrova [Suisse] ; Angelika M. Vollmar [Allemagne] ; Stefan Zahler [Allemagne]

Source :

Nature communications [ 2041-1723 ] ; 2015.

RBID : pubmed:26027726

Descripteurs français

English descriptors

KwdEn :
- Animals, Cyclin-Dependent Kinase 5 (genetics), Cyclin-Dependent Kinase 5 (metabolism), Endothelial Cells (cytology), Endothelial Cells (metabolism), Forkhead Transcription Factors (genetics), Forkhead Transcription Factors (metabolism), Human Umbilical Vein Endothelial Cells, Humans, Lymphangiogenesis (genetics), Lymphatic Vessels (metabolism), Lymphatic Vessels (pathology), Mice, Mice, Knockout, Phosphorylation, Real-Time Polymerase Chain Reaction, Stress, Mechanical.
MESH :
- chemical , genetics : Cyclin-Dependent Kinase 5, Forkhead Transcription Factors.
- chemical , metabolism : Cyclin-Dependent Kinase 5, Forkhead Transcription Factors.
- cytology : Endothelial Cells.
- genetics : Lymphangiogenesis.
- metabolism : Endothelial Cells, Lymphatic Vessels.
- pathology : Lymphatic Vessels.
- Animals, Human Umbilical Vein Endothelial Cells, Humans, Mice, Mice, Knockout, Phosphorylation, Real-Time Polymerase Chain Reaction, Stress, Mechanical.

Abstract

The lymphatic system maintains tissue fluid balance, and dysfunction of lymphatic vessels and valves causes human lymphedema syndromes. Yet, our knowledge of the molecular mechanisms underlying lymphatic vessel development is still limited. Here, we show that cyclin-dependent kinase 5 (Cdk5) is an essential regulator of lymphatic vessel development. Endothelial-specific Cdk5 knockdown causes congenital lymphatic dysfunction and lymphedema due to defective lymphatic vessel patterning and valve formation. We identify the transcription factor Foxc2 as a key substrate of Cdk5 in the lymphatic vasculature, mechanistically linking Cdk5 to lymphatic development and valve morphogenesis. Collectively, our findings show that Cdk5-Foxc2 interaction represents a critical regulator of lymphatic vessel development and the transcriptional network underlying lymphatic vascular remodeling.

DOI: 10.1038/ncomms8274
PubMed: 26027726

Affiliations:

Le document en format XML

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<term>Endothelial Cells (cytology)</term>
<term>Endothelial Cells (metabolism)</term>
<term>Forkhead Transcription Factors (genetics)</term>
<term>Forkhead Transcription Factors (metabolism)</term>
<term>Human Umbilical Vein Endothelial Cells</term>
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<term>Lymphangiogenesis (genetics)</term>
<term>Lymphatic Vessels (metabolism)</term>
<term>Lymphatic Vessels (pathology)</term>
<term>Mice</term>
<term>Mice, Knockout</term>
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<term>Real-Time Polymerase Chain Reaction</term>
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<term>Cellules endothéliales (métabolisme)</term>
<term>Cellules endothéliales de la veine ombilicale humaine</term>
<term>Contrainte mécanique</term>
<term>Facteurs de transcription Forkhead (génétique)</term>
<term>Facteurs de transcription Forkhead (métabolisme)</term>
<term>Humains</term>
<term>Kinase-5 cycline-dépendante (génétique)</term>
<term>Kinase-5 cycline-dépendante (métabolisme)</term>
<term>Lymphangiogenèse (génétique)</term>
<term>Phosphorylation</term>
<term>Réaction de polymérisation en chaine en temps réel</term>
<term>Souris</term>
<term>Souris knockout</term>
<term>Vaisseaux lymphatiques (anatomopathologie)</term>
<term>Vaisseaux lymphatiques (métabolisme)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Cyclin-Dependent Kinase 5</term>
<term>Forkhead Transcription Factors</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Cyclin-Dependent Kinase 5</term>
<term>Forkhead Transcription Factors</term>
</keywords>
<keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Vaisseaux lymphatiques</term>
</keywords>
<keywords scheme="MESH" qualifier="cytologie" xml:lang="fr"><term>Cellules endothéliales</term>
</keywords>
<keywords scheme="MESH" qualifier="cytology" xml:lang="en"><term>Endothelial Cells</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Lymphangiogenesis</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Facteurs de transcription Forkhead</term>
<term>Kinase-5 cycline-dépendante</term>
<term>Lymphangiogenèse</term>
</keywords>
<keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Endothelial Cells</term>
<term>Lymphatic Vessels</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Cellules endothéliales</term>
<term>Facteurs de transcription Forkhead</term>
<term>Kinase-5 cycline-dépendante</term>
<term>Vaisseaux lymphatiques</term>
</keywords>
<keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Lymphatic Vessels</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Animals</term>
<term>Human Umbilical Vein Endothelial Cells</term>
<term>Humans</term>
<term>Mice</term>
<term>Mice, Knockout</term>
<term>Phosphorylation</term>
<term>Real-Time Polymerase Chain Reaction</term>
<term>Stress, Mechanical</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Animaux</term>
<term>Cellules endothéliales de la veine ombilicale humaine</term>
<term>Contrainte mécanique</term>
<term>Humains</term>
<term>Phosphorylation</term>
<term>Réaction de polymérisation en chaine en temps réel</term>
<term>Souris</term>
<term>Souris knockout</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">The lymphatic system maintains tissue fluid balance, and dysfunction of lymphatic vessels and valves causes human lymphedema syndromes. Yet, our knowledge of the molecular mechanisms underlying lymphatic vessel development is still limited. Here, we show that cyclin-dependent kinase 5 (Cdk5) is an essential regulator of lymphatic vessel development. Endothelial-specific Cdk5 knockdown causes congenital lymphatic dysfunction and lymphedema due to defective lymphatic vessel patterning and valve formation. We identify the transcription factor Foxc2 as a key substrate of Cdk5 in the lymphatic vasculature, mechanistically linking Cdk5 to lymphatic development and valve morphogenesis. Collectively, our findings show that Cdk5-Foxc2 interaction represents a critical regulator of lymphatic vessel development and the transcriptional network underlying lymphatic vascular remodeling.</div>
</front>
</TEI>
<affiliations><list><country><li>Allemagne</li>
<li>Japon</li>
<li>Suisse</li>
<li>États-Unis</li>
</country>
<region><li>Bavière</li>
<li>Canton de Vaud</li>
<li>District de Haute-Bavière</li>
<li>District de Münster</li>
<li>Rhénanie-du-Nord-Westphalie</li>
</region>
<settlement><li>Lausanne</li>
<li>Munich</li>
<li>Münster</li>
</settlement>
<orgName><li>Université Louis-et-Maximilien de Munich</li>
</orgName>
</list>
<tree><country name="Allemagne"><region name="Bavière"><name sortKey="Liebl, Johanna" sort="Liebl, Johanna" uniqKey="Liebl J" first="Johanna" last="Liebl">Johanna Liebl</name>
</region>
<name sortKey="Adams, Ralf H" sort="Adams, Ralf H" uniqKey="Adams R" first="Ralf H" last="Adams">Ralf H. Adams</name>
<name sortKey="Hager, Bianca" sort="Hager, Bianca" uniqKey="Hager B" first="Bianca" last="Hager">Bianca Hager</name>
<name sortKey="Kiefer, Friedemann" sort="Kiefer, Friedemann" uniqKey="Kiefer F" first="Friedemann" last="Kiefer">Friedemann Kiefer</name>
<name sortKey="Moser, Markus" sort="Moser, Markus" uniqKey="Moser M" first="Markus" last="Moser">Markus Moser</name>
<name sortKey="Vollmar, Angelika M" sort="Vollmar, Angelika M" uniqKey="Vollmar A" first="Angelika M" last="Vollmar">Angelika M. Vollmar</name>
<name sortKey="Zahler, Stefan" sort="Zahler, Stefan" uniqKey="Zahler S" first="Stefan" last="Zahler">Stefan Zahler</name>
<name sortKey="Zhang, Siwei" sort="Zhang, Siwei" uniqKey="Zhang S" first="Siwei" last="Zhang">Siwei Zhang</name>
</country>
<country name="Suisse"><noRegion><name sortKey="Agalarov, Yan" sort="Agalarov, Yan" uniqKey="Agalarov Y" first="Yan" last="Agalarov">Yan Agalarov</name>
</noRegion>
<name sortKey="Demir, Cansaran Saygili" sort="Demir, Cansaran Saygili" uniqKey="Demir C" first="Cansaran Saygili" last="Demir">Cansaran Saygili Demir</name>
<name sortKey="Petrova, Tatiana V" sort="Petrova, Tatiana V" uniqKey="Petrova T" first="Tatiana V" last="Petrova">Tatiana V. Petrova</name>
</country>
<country name="États-Unis"><noRegion><name sortKey="Bibb, James A" sort="Bibb, James A" uniqKey="Bibb J" first="James A" last="Bibb">James A. Bibb</name>
</noRegion>
</country>
<country name="Japon"><noRegion><name sortKey="Miura, Naoyuki" sort="Miura, Naoyuki" uniqKey="Miura N" first="Naoyuki" last="Miura">Naoyuki Miura</name>
</noRegion>
</country>
</tree>
</affiliations>
</record>

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Serveur d'exploration sur le lymphœdème

Cdk5 controls lymphatic vessel development and function by phosphorylation of Foxc2.

Cdk5 controls lymphatic vessel development and function by phosphorylation of Foxc2.

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