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

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State: Public
Version: Final published version
Serval ID
serval:BIB_3B60F81231F4
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Cdk5 controls lymphatic vessel development and function by phosphorylation of Foxc2.
Journal
Nature Communications
Author(s)
Liebl J., Zhang S., Moser M., Agalarov Y., Demir C.S., Hager B., Bibb J.A., Adams R.H., Kiefer F., Miura N., Petrova T.V., Vollmar A.M., Zahler S.
ISSN
2041-1723 (Electronic)
ISSN-L
2041-1723
Publication state
Published
Issued date
2015
Peer-reviewed
Oui
Volume
6
Pages
7274
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
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.
Keywords
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
Pubmed
Web of science
Open Access
Yes
Create date
24/07/2015 7:07
Last modification date
20/08/2019 13:31
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