2. Academic Validation
  3. Venous identity requires BMP signalling through ALK3

Venous identity requires BMP signalling through ALK3

  • Nat Commun. 2019 Jan 28;10(1):453. doi: 10.1038/s41467-019-08315-w.
Alice Neal 1 2,  Svanhild Nornes 1 2,  Sophie Payne 1,  Marsha D Wallace 1,  Martin Fritzsche 1,  Pakavarin Louphrasitthiphol 1,  Robert N Wilkinson 3,  Kira M Chouliaras 1,  Ke Liu 4,  Karen Plant 3,  Radhika Sholapurkar 1,  Indrika Ratnayaka 1,  Wiebke Herzog 5 6,  Gareth Bond 1,  Tim Chico 3,  George Bou-Gharios 4,  Sarah De Val 7 8
Affiliations

Affiliations

  • 1 Ludwig Institute for Cancer Research Ltd, Nuffield Department of Medicine, University of Oxford, Oxford, OX3 7DQ, UK.
  • 2 Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, OX1 3PT, UK.
  • 3 Department of Infection, Immunity and Cardiovascular Disease and Bateson Centre, University of Sheffield, Sheffield, S10 2TN, UK.
  • 4 Institute of Aging and Chronic Disease, University of Liverpool, Liverpool, L7 8TX, UK.
  • 5 University of Muenster, Schlossplatz 2, Muenster, 48149, Germany.
  • 6 Cells-in Motion Cluster of Excellence EXC1003-CiM, University of Muenster, Waldeyerstraße 15, Muenster, 48149, Germany.
  • 7 Ludwig Institute for Cancer Research Ltd, Nuffield Department of Medicine, University of Oxford, Oxford, OX3 7DQ, UK. sarah.deval@dpag.ox.ac.uk.
  • 8 Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, OX1 3PT, UK. sarah.deval@dpag.ox.ac.uk.
PMID: 30692543 DOI: 10.1038/s41467-019-08315-w
Abstract

Venous endothelial cells are molecularly and functionally distinct from their arterial counterparts. Although veins are often considered the default endothelial state, genetic manipulations can modulate both acquisition and loss of venous fate, suggesting that venous identity is the result of active transcriptional regulation. However, little is known about this process. Here we show that BMP signalling controls venous identity via the ALK3/BMPR1A receptor and SMAD1/SMAD5. Perturbations to TGF-β and BMP signalling in mice and zebrafish result in aberrant vein formation and loss of expression of the venous-specific gene EphB4, with no effect on arterial identity. Analysis of a venous endothelium-specific enhancer for EphB4 shows enriched binding of SMAD1/5 and a requirement for SMAD binding motifs. Further, our results demonstrate that BMP/SMAD-mediated EphB4 expression requires the venous-enriched BMP type I receptor ALK3/BMPR1A. Together, our analysis demonstrates a requirement for BMP signalling in the establishment of EphB4 expression and the venous vasculature.

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