BMP-SMAD signalling output is highly regionalized in cardiovascular and lymphatic endothelial networks

Background Bone morphogenetic protein (BMP) signalling has emerged as a fundamental pathway in endothelial cell biology and deregulation of this pathway is implicated in several vascular disorders. BMP signalling output in endothelial cells is highly context- and dose-dependent. Phosphorylation of the BMP intracellular effectors, SMAD1/5/9, is routinely used to monitor BMP signalling activity. To better understand the in vivo context-dependency of BMP-SMAD signalling, we investigated differences in BMP-SMAD transcriptional activity in different vascular beds during mouse embryonic and postnatal stages. For this, we used the BRE::gfp BMP signalling reporter mouse in which the BMP response element (BRE) from the ID1-promotor, a SMAD1/5/9 target gene, drives the expression of GFP. Results A mosaic pattern of GFP was present in various angiogenic sprouting plexuses and in endocardium of cardiac cushions and trabeculae in the heart. High calibre veins seemed to be more BRE::gfp transcriptionally active than arteries, and ubiquitous activity was present in embryonic lymphatic vasculature. Postnatal lymphatic vessels showed however only discrete micro-domains of transcriptional activity. Dynamic shifts in transcriptional activity were also observed in the endocardium of the developing heart, with a general decrease in activity over time. Surprisingly, proliferative endothelial cells were almost never GFP-positive. Patches of transcriptional activity seemed to correlate with vasculature undergoing hemodynamic alterations. Conclusion The BRE::gfp mouse allows to investigate selective context-dependent aspects of BMP-SMAD signalling. Our data reveals the highly dynamic nature of BMP-SMAD mediated transcriptional regulation in time and space throughout the vascular tree, supporting that BMP-SMAD signalling can be a source of phenotypic diversity in some, but not all, healthy endothelium. This knowledge can provide insight in vascular bed or organ-specific diseases and phenotypic heterogeneity within an endothelial cell population. Electronic supplementary material The online version of this article (doi:10.1186/s12861-016-0133-x) contains supplementary material, which is available to authorized users.

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PID urn:URN:NBN:NL:UI:26-1887/95215
PID handle:1887/95215
PID https://www.doi.org/10.1186/s12861-016-0133-x
PID pmid:27724845
PID pmc:PMC5057272
URL http://dx.doi.org/10.1186/s12861-016-0133-x
URL https://bmcdevbiol.biomedcentral.com/track/pdf/10.1186/s12861-016-0133-x
URL https://link.springer.com/article/10.1186/s12861-016-0133-x
URL http://link.springer.com/content/pdf/10.1186/s12861-016-0133-x.pdf
URL https://bmcdevbiol.biomedcentral.com/track/pdf/10.1186/s12861-016-0133-x?site=bmcdevbiol.biomedcentral.com
URL https://academic.microsoft.com/#/detail/2530229975
URL http://europepmc.org/articles/PMC5057272
URL https://dx.doi.org/10.1186/s12861-016-0133-x
URL https://lirias.kuleuven.be/handle/123456789/553922
URL https://paperity.org/p/78166355/bmp-smad-signalling-output-is-highly-regionalized-in-cardiovascular-and-lymphatic
URL http://www.ncbi.nlm.nih.gov/pubmed/27724845
URL http://bmcdevbiol.biomedcentral.com/articles/10.1186/s12861-016-0133-x
URL https://core.ac.uk/display/81861194
URL http://hdl.handle.net/1887/95215
URL https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5057272
URL https://bmcdevbiol.biomedcentral.com/articles/10.1186/s12861-016-0133-x
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Author Beets, Karen
Author Staring, Michael W.
Author Criem, Nathan
Author Maas, Elke
Author Schellinx, Niels
Author de Sousa Lopes, Susana M. Chuva
Author Umans, Lieve
Author Zwijsen, An, 0000-0002-8583-1721
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Collected From Europe PubMed Central; PubMed Central; ORCID; Datacite; UnpayWall; NARCIS; Crossref; Lirias; Microsoft Academic Graph; CORE (RIOXX-UK Aggregator)
Hosted By Europe PubMed Central; SpringerOpen; Leiden University Repository; BMC Developmental Biology; NARCIS; Lirias
Publication Date 2016-10-01
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Country Netherlands; Belgium
Format application/pdf; Electronic
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Resource Type Article; UNKNOWN
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Source https://science-innovation-policy.openaire.eu/search/publication?articleId=dedup_wf_001::b603dd7affaab40f9fe8ecf89cedf3ba
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Last Updated 24 December 2020, 23:27 (CET)
Created 24 December 2020, 23:27 (CET)