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          Institute: MPI für molekulare Biomedizin     Collection: Jahrbuch 2016 (publ. 2015, arch)     Display Documents



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ID: 717296.0, MPI für molekulare Biomedizin / Jahrbuch 2016 (publ. 2015, arch)
Cdk5 controls lymphatic vessel development and function by phosphorylation of Foxc2
Authors: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.
Date of Publication (YYYY-MM-DD):2015
Title of Journal:Nat Commun
Volume:6
Start Page:7274
Review Status:Internal review
Audience:Not Specified
Abstract / Description: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.
External Publication Status:published
Document Type:Article
Communicated by:Keuker
Affiliations:MPI für molekulare Biomedizin
External Affiliations:Department of Molecular Medicine, Max Planck Institute of Biochemistry, 81377 Martinsried, Germany. Department of Oncology, University Hospital of Lausanne, and Department of Biochemistry, University of Lausanne, 1066 Epalinges, Switzerland. Department of Psychiatry and Neurology and Neurotherapeutics, The University of Texas Southwestern Medical Center, Dallas, Texas 75390-9070, USA. 1] Department of Tissue Morphogenesis, Max Planck Institute for Molecular Biomedicine, 48149 Munster, Germany [2] University of Munster, Faculty of Medicine, 48149 Munster, Germany. Mammalian Cell Signaling Laboratory, Department of Vascular Cell Biology, Max Planck Institute for Molecular Biomedicine, 48149 Munster, Germany. Department of Biochemistry, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan. 1] Department of Oncology, University Hospital of Lausanne, and Department of Biochemistry, University of Lausanne, 1066 Epalinges, Switzerland [2] Ecole Polytechnique Federale de Lausanne (EPFL), Swiss Institute for Experimental Cancer Research (ISREC), 1015 Lausanne, Switzerland.
Identifiers:ISSN:2041-1723 (Electronic) 2041-1723 (Linking) %R 10.1... [ID No:1]
URL:http://www.ncbi.nlm.nih.gov/pubmed/26027726 [ID No:2]
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