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  Cdk5 controls lymphatic vessel development and function by phosphorylation of Foxc2

Liebl, J., Zhang, S., Moser, M., Agalarov, Y., Demir, C. S., Hager, B., et al. (2015). Cdk5 controls lymphatic vessel development and function by phosphorylation of Foxc2. NATURE COMMUNICATIONS, 6: 7274. doi:10.1038/ncomms8274.

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 Creators:
Liebl, Johanna1, Author
Zhang, Siwei1, Author
Moser, Markus2, Author              
Agalarov, Yan1, Author
Demir, Cansaran Saygili1, Author
Hager, Bianca1, Author
Bibb, James A.1, Author
Adams, Ralf H.1, Author
Kiefer, Friedemann1, Author
Miura, Naoyuki1, Author
Petrova, Tatiana V.1, Author
Vollmar, Angelika M.1, Author
Zahler, Stefan1, Author
Affiliations:
1external, ou_persistent22              
2Fässler, Reinhard / Molecular Medicine, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565147              

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Free keywords: CYCLIN-DEPENDENT KINASE-5; LYMPHEDEMA-DISTICHIASIS SYNDROME; ENDOTHELIAL-CELL MIGRATION; VALVE FORMATION; VASCULAR MORPHOGENESIS; TRANSCRIPTION FACTOR; ACTIVATOR P35NCK5A; MONOCYTIC CELLS; BLOOD; MICE
 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.

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Language(s): eng - English
 Dates: 2015
 Publication Status: Published online
 Pages: 13
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: ISI: 000357170800001
DOI: 10.1038/ncomms8274
 Degree: -

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Title: NATURE COMMUNICATIONS
Source Genre: Journal
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Publ. Info: MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND : NATURE PUBLISHING GROUP
Pages: - Volume / Issue: 6 Sequence Number: 7274 Start / End Page: - Identifier: ISSN: 2041-1723