Cdk5 controls lymphatic vessel development and function by phosphorylation of Foxc2

Johanna Liebl (), Siwei Zhang, Markus Moser, Yan Agalarov, Cansaran Saygili Demir, Bianca Hager, James A. Bibb, Ralf H. Adams, Friedemann Kiefer, Naoyuki Miura, Tatiana V. Petrova, Angelika M. Vollmar and Stefan Zahler
Additional contact information
Johanna Liebl: Pharmaceutical Biology, Ludwig-Maximilians-University
Siwei Zhang: Pharmaceutical Biology, Ludwig-Maximilians-University
Markus Moser: Max Planck Institute of Biochemistry
Yan Agalarov: University Hospital of Lausanne, University of Lausanne
Cansaran Saygili Demir: University Hospital of Lausanne, University of Lausanne
Bianca Hager: Pharmaceutical Biology, Ludwig-Maximilians-University
James A. Bibb: The University of Texas Southwestern Medical Center
Ralf H. Adams: Max Planck Institute for Molecular Biomedicine
Friedemann Kiefer: Mammalian Cell Signaling Laboratory, Max Planck Institute for Molecular Biomedicine
Naoyuki Miura: Hamamatsu University School of Medicine
Tatiana V. Petrova: University Hospital of Lausanne, University of Lausanne
Angelika M. Vollmar: Pharmaceutical Biology, Ludwig-Maximilians-University
Stefan Zahler: Pharmaceutical Biology, Ludwig-Maximilians-University

Nature Communications, 2015, vol. 6, issue 1, 1-13

Abstract: 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.

Date: 2015
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/ncomms8274 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms8274

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms8274

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().