Venous identity requires BMP signalling through ALK3

Alice Neal, Svanhild Nornes, Sophie Payne, Marsha D Wallace, Martin Fritzsche, Pakavarin Louphrasitthiphol, Robert N Wilkinson, Kira M Chouliaras, Ke Liu, Karen Plant, Radhika Sholapurkar, Indrika Ratnayaka, Wiebke Herzog, Gareth Bond, Tim Chico, George Bou-Gharios, Sarah De Val

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)
105 Downloads (Pure)


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.

Original languageEnglish
Article number453
Pages (from-to)1-18
Number of pages18
JournalNature Communications
Publication statusPublished - 28 Jan 2019


  • Animals
  • Animals, Genetically Modified
  • Bone Morphogenetic Protein Receptors, Type I/genetics
  • Bone Morphogenetic Proteins/genetics
  • Endothelial Cells/metabolism
  • Gene Expression Regulation, Developmental
  • Mice, Knockout
  • Mice, Transgenic
  • Receptor, EphB4/genetics
  • Signal Transduction/genetics
  • Smad1 Protein/genetics
  • Smad5 Protein/genetics
  • Transforming Growth Factor beta/genetics
  • Veins/embryology
  • Zebrafish/embryology
  • Zebrafish Proteins/genetics


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