Evidence map›Paper›PMID 27724845›Full record

ArticleBMC developmental biology2016

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

Karen Beets, Michael W Staring, Nathan Criem, Elke Maas, Niels Schellinx, Susana M Chuva de Sousa Lopes, Lieve Umans, An Zwijsen

Open access · hybridAbstract read
In one paragraph

Article in BMC developmental biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.2field-weighted citation impact, top 19% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

13 citing papers in PubMed, 22 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. The BMP Pathway in Blood Vessel and Lymphatic Vessel Biology.International journal of molecular sciences · 2021
    Review
  7. Review
  8. Cell Fate Determination of Lymphatic Endothelial Cells.International journal of molecular sciences · 2020
    Review
  9. Article
  10. Article
  11. The TGFβ superfamily in cardiac dysfunction.Acta biochimica et biophysica Sinica · 2018
    Review
  12. Article
  13. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 2 countries.

Karen BeetsVIB Center for the Biology of Disease, VIB, Leuven, Belgium.
Michael W StaringVIB Center for the Biology of Disease, VIB, Leuven, Belgium.
Nathan CriemVIB Center for the Biology of Disease, VIB, Leuven, Belgium.
Elke MaasVIB Center for the Biology of Disease, VIB, Leuven, Belgium.
Niels SchellinxVIB Center for the Biology of Disease, VIB, Leuven, Belgium.
Susana M Chuva de Sousa LopesDepartment Anatomy and Embryology, Leiden University Medical Centre, Leiden, The Netherlands.
Lieve UmansVIB Center for the Biology of Disease, VIB, Leuven, Belgium.
An ZwijsenVIB Center for the Biology of Disease, VIB, Leuven, Belgium. an.zwijsen@cme.vib-kuleuven.be.ORCID 0000-0002-8583-1721
VIB-KU Leuven Center for Cancer Biology · BELeiden University · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundBone 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.

resultsA 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.

conclusionThe 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.

Indexed as

Gene Regulatory NetworksAnimalsAnimals, NewbornBone Morphogenetic ProteinsCardiovascular SystemEmbryo, MammalianEndocardiumEndothelial CellsGene Expression Regulation, DevelopmentalGreen Fluorescent ProteinsMiceMice, TransgenicPhosphorylationSignal TransductionSmad ProteinsTranscriptional ActivationBone Morphogenetic ProteinsGreen Fluorescent ProteinsSmad ProteinsBMP-SMAD signallingEndocardiumHeterogeneityLymphangiogenesisMorphogenPhenotype switchingRetinaSprouting angiogenesisStochastic expressionValve development

Identifiers

PMID27724845
PMCPMC5057272
OpenAlexW2530229975

What OpenQuestion holds

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LicenceCC BY
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.