Evidence map›Paper›PMID 23818617›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2013

Analysis of Dll4 regulation reveals a combinatorial role for Sox and Notch in arterial development.

Natalia Sacilotto, Rui Monteiro, Martin Fritzsche, Philipp W Becker, Luis Sanchez-Del-Campo, Ke Liu, Philip Pinheiro, Indrika Ratnayaka, Benjamin Davies, Colin R Goding and 3 more

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers.

0numbers the graph read from it
0cells of the map it votes in
86citing papers in PubMed
5.7field-weighted citation impact, top 4% 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

86 citing papers in PubMed, 134 citations in OpenAlex.

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  16. The evolving hematopoietic niche during development.Frontiers in molecular biosciences · 2024
    Review
  17. Transcription factors regulating vasculogenesis and angiogenesis.Developmental dynamics : an official publication of the American Association of Anatomists · 2024
    Review
  18. Review
  19. Article
  20. Review

26 more citing papers are in PubMed but not listed here.

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

13 authors at 5 institutions in 1 country.

Natalia SacilottoLudwig Institute for Cancer Research Ltd, Nuffield Department of Clinical Medicine, University of Oxford, Oxford OX3 7DQ, United Kingdom.
Rui Monteiro
Martin Fritzsche
Philipp W Becker
Luis Sanchez-Del-Campo
Ke Liu
Philip Pinheiro
Indrika Ratnayaka
Benjamin Davies
Colin R Goding
Roger Patient
George Bou-Gharios
Sarah De Val
University of Oxford · GBLudwig Cancer Research · GBBritish Heart Foundation · GBCentre for Human Genetics · GBJohn Radcliffe Hospital · GB

Funding

British Heart Foundation PG/09/082/28020British Heart Foundation PG/10/83/28610British Heart Foundation RE/08/004Medical Research Council MC_U137981013Medical Research Council MC_UU_12009/8Medical Research Council MR/J007765/1Wellcome Trust 090532
6 · The paper itself

Abstract

The mechanisms by which arterial fate is established and maintained are not clearly understood. Although a number of signaling pathways and transcriptional regulators have been implicated in arterio-venous differentiation, none are essential for arterial formation, and the manner in which widely expressed factors may achieve arterial-specific gene regulation is unclear. Using both mouse and zebrafish models, we demonstrate here that arterial specification is regulated combinatorially by Notch signaling and SoxF transcription factors, via direct transcriptional gene activation. Through the identification and characterization of two arterial endothelial cell-specific gene enhancers for the Notch ligand Delta-like ligand 4 (Dll4), we show that arterial Dll4 expression requires the direct binding of both the RBPJ/Notch intracellular domain and SOXF transcription factors. Specific combinatorial, but not individual, loss of SOXF and RBPJ DNA binding ablates all Dll4 enhancer-transgene expression despite the presence of multiple functional ETS binding sites, as does knockdown of sox7;sox18 in combination with loss of Notch signaling. Furthermore, triple knockdown of sox7, sox18 and rbpj also results in ablation of endogenous dll4 expression. Fascinatingly, this combinatorial ablation leads to a loss of arterial markers and the absence of a detectable dorsal aorta, demonstrating the essential roles of SoxF and Notch, together, in the acquisition of arterial identity.

Indexed as

Adaptor Proteins, Signal TransducingAnimalsArteriesCalcium-Binding ProteinsChromatin ImmunoprecipitationCloning, MolecularElectrophoretic Mobility Shift AssayGene Expression Regulation, DevelopmentalGene Knockdown TechniquesImmunoglobulin J Recombination Signal Sequence-Binding ProteinImmunohistochemistryIn Situ HybridizationIntracellular Signaling Peptides and ProteinsMembrane ProteinsMiceMice, TransgenicAdaptor Proteins, Signal TransducingCalcium-Binding ProteinsDLL4 protein, mouseImmunoglobulin J Recombination Signal Sequence-Binding ProteinIntracellular Signaling Peptides and ProteinsMembrane ProteinsRbpj protein, mouseReceptors, NotchSOXF Transcription Factorsarterial-specific enhancerCSL

Identifiers

PMID23818617
PMCPMC3718163
OpenAlexW1964018614

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.