Cdk5 controls lymphatic vessel development and function by phosphorylation of Foxc2

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. Vollmar, Stefan Zahler

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

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.

Original languageEnglish (US)
Article number7274
JournalNature communications
Volume6
DOIs
StatePublished - Jun 1 2015

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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