BMP-SMAD signalling output is highly regionalized in cardiovascular and lymphatic endothelial networks. Issue 1 (December 2016)

• Record Type: Journal Article
• Authors: Beets, Karen; Staring, Michael; Criem, Nathan; Maas, Elke; Schellinx, Niels; de Sousa Lopes, Susana; Umans, Lieve; Zwijsen, An
• Is Part Of: BMC developmental biology. Volume 16:Issue 1(2016)
• Page Start: 1
• Page End: 16
• Publication Date: 2016-12
• Subjects: BMP-SMAD signalling -- Sprouting angiogenesis -- Valve development -- Lymphangiogenesis -- Endocardium -- Phenotype switching -- Heterogeneity -- Retina -- Stochastic expression -- Morphogen; Developmental biology -- Periodicals; 571.8
• DOI: 10.1186/s12861-016-0133-x
• Languages: English
• ISSNs: 1471-213X

Abstract

Abstract 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 theBRE ::gfp BMP signalling reporter mouse in which the BMP response element (BRE) from theID1 -promotor, a SMAD1/5/9 target gene, drives the expression ofGFP . 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 moreBRE ::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 TheBRE ::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.