@article{6ceecb513ec448d1ae73cc9dec9a4264,
title = "Cdk5 controls lymphatic vessel development and function by phosphorylation of Foxc2",
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.",
author = "Johanna Liebl and Siwei Zhang and Markus Moser and Yan Agalarov and Demir, {Cansaran Saygili} and Bianca Hager and Bibb, {James A.} and Adams, {Ralf H.} and Friedemann Kiefer and Naoyuki Miura and Petrova, {Tatiana V.} and Vollmar, {Angelika M.} and Stefan Zahler",
note = "Funding Information: We thank Paul Greengard (Rockefeller University) for providing the floxed Cdk5 mice. We thank Amelie Sabine for helping with valve quantification, Helene Maby-El Hajjami for the LEC/BEC isolation protocol (EPFL, ISREC, University of Lausanne). We thank Ashok B. Kulkarni and Michaela Prochazkova (NIH/NIDCR) for providing tissues from standard Cdk5 knockout embryos. We thank Cathrin Pollmann (MPI Molecular Biomedicine, M{\"u}nster, Germany) for help with lymphovenous valve staining. We thank Kerstin Loske and Jana Peliskova for mouse genotyping and help with biochemical experiments, Rita Socher and Anna Kulinyak for preparing paraffin sections (Department of Pharmacy, LMU Munich). The animal facility of the Department of Pharmacy, LMU Munich is gratefully acknowledged. This work was supported by German Research Foundation (ZA 186/4-1, to S.Z.) and CRSII3_141811 (to T.V.P.). This work was supported by Swiss National Science Foundation (PPP0033-114898 and CRSII3-141811 to T.V.P.) and the People Programme (Marie Curie Actions) of the European Union{\textquoteright}s Seventh Framework Programme FP7/2007–2013/ under REA grant agreement 317250 (C.S.D). Publisher Copyright: {\textcopyright} 2015 Macmillan Publishers Limited. All rights reserved.",
year = "2015",
month = jun,
day = "1",
doi = "10.1038/ncomms8274",
language = "English (US)",
volume = "6",
journal = "Nature communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
}