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Cdk5 controls lymphatic vessel development and function by phosphorylation of Foxc2

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Listed:
  • 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
    University of Münster, Faculty of Medicine)

  • 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
    Ecole Polytechnique Federale de Lausanne (EPFL), Swiss Institute for Experimental Cancer Research (ISREC))

  • Angelika M. Vollmar

    (Pharmaceutical Biology, Ludwig-Maximilians-University)

  • Stefan Zahler

    (Pharmaceutical Biology, Ludwig-Maximilians-University)

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.

Suggested Citation

  • 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., 2015. "Cdk5 controls lymphatic vessel development and function by phosphorylation of Foxc2," Nature Communications, Nature, vol. 6(1), pages 1-13, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms8274
    DOI: 10.1038/ncomms8274
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