Venous identity requires BMP signalling through ALK3

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.

Metadata

Item Type:	Article
Authors/Creators:	Neal, A. Nornes, S. Payne, S. Wallace, M.D. Fritzsche, M. Louphrasitthiphol, P. Wilkinson, R.N. https://orcid.org/0000-0003-2706-316X Chouliaras, K.M. Liu, K. Plant, K. Sholapurkar, R. Ratnayaka, I. Herzog, W. Bond, G. Chico, T. https://orcid.org/0000-0002-7458-5481 Bou-Gharios, G. De Val, S.
Copyright, Publisher and Additional Information:	© The Author(s) 2019. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Dates:	Accepted: 20 December 2018 Published (online): 28 January 2019 Published: 28 January 2019
Institution:	The University of Sheffield
Academic Units:	The University of Sheffield > Sheffield Teaching Hospitals
Depositing User:	Symplectic Sheffield
Date Deposited:	15 Feb 2019 11:02
Last Modified:	15 Feb 2019 11:02
Published Version:	https://doi.org/10.1038/s41467-019-08315-w
Status:	Published
Publisher:	Nature Research
Refereed:	Yes
Identification Number:	10.1038/s41467-019-08315-w
Related URLs:	PubMed URL
Open Archives Initiative ID (OAI ID):	oai:eprints.whiterose.ac.uk:142456

Download

Published Version

Filename: s41467-019-08315-w.pdf

Licence: CC-BY 4.0

CLICK TO DOWNLOAD

CORE (COnnecting REpositories)

Venous identity requires BMP signalling through ALK3

Abstract

Metadata

Download

Published Version

Export

Statistics