Evidence map›Paper›PMID 22076636›Full record

ArticleCirculation research2012

Integration of repulsive guidance cues generates avascular zones that shape mammalian blood vessels.

Stryder M Meadows, Peter J Fletcher, Carlos Moran, Ke Xu, Gera Neufeld, Sophie Chauvet, Fanny Mann, Paul A Krieg, Ondine Cleaver

Open access · bronzeAbstract read
In one paragraph

Article in Circulation research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
2.4field-weighted citation impact, top 12% 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

37 citing papers in PubMed, 63 citations in OpenAlex.

  1. Article
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  7. Transcription Landscape of the Early Developmental Biology in Pigs.Animals : an open access journal from MDPI · 2021
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  11. Review
  12. Review
  13. Review
  14. Role of Semaphorin Signaling During Cardiovascular Development.Journal of the American Heart Association · 2018
    Review
  15. Article
  16. Article
  17. The role of the semaphorins in cancer.Cell adhesion & migration · 2016
    Review
  18. Review
  19. Blood vessel crosstalk during organogenesis-focus on pancreas and endothelial cells.Wiley interdisciplinary reviews. Developmental biology · 2016
    Review
  20. Article
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

9 authors at 2 institutions in 2 countries.

Stryder M MeadowsDepartment of Molecular Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, NA8.300, Dallas, TX 75390-9148, USA.
Peter J Fletcher
Carlos Moran
Ke Xu
Gera Neufeld
Sophie Chauvet
Fanny Mann
Paul A Krieg
Ondine Cleaver
Technion – Israel Institute of Technology · ILUniversity of Arizona · US

Funding

TRAINING IN CARDIOVASCULAR RESEARCHT32HL007360 · NHLBI · UT SOUTHWESTERN MEDICAL CENTER · PI HILL, JOSEPH A · 1985 to 2012
$11.8M
Embryonic Blood Vessel FormationR01HL074184 · NHLBI · UNIVERSITY OF ARIZONA · PI KRIEG, PAUL ANTHONY · 2003 to 2007
$1.7M
Blood vessel tubulogenesis: Rasip1-directed GTPase signaling and cell polarity.R01HL113498 · NHLBI · UT SOUTHWESTERN MEDICAL CENTER · PI CLEAVER, ONDINE B · 2012 to 2015
$1.7M
Endothelial Signals During OrganogenesisR01DK079862 · NIDDK · UT SOUTHWESTERN MEDICAL CENTER · PI CLEAVER, ONDINE B · 2007 to 2011
$1.5M
NHLBI NIH HHS HL007360-32NHLBI NIH HHS HL074184-02NHLBI NIH HHS R01 HL074184NHLBI NIH HHS R01 HL113498NHLBI NIH HHS T32 HL007360NIDDK NIH HHS DK079862NIDDK NIH HHS R01 DK079862
6 · The paper itself

Abstract

rationalePositive signals, such as vascular endothelial growth factor, direct endothelial cells (ECs) to specific locations during blood vessel formation. Less is known about repulsive signal contribution to shaping vessels. Recently, "neuronal guidance cues" have been shown to influence EC behavior, particularly in directing sprouting angiogenesis by repelling ECs. However, their role during de novo blood vessel formation remains unexplored.

objectiveTo identify signals that guide and pattern the first mammalian blood vessels. METHODS AND

resultsUsing genetic mouse models, we show that blood vessels are sculpted through the generation of stereotyped avascular zones by EC-repulsive cues. We demonstrate that Semaphorin3E (Sema3E) is a key factor that shapes the paired dorsal aortae in mouse, as sema3E(-/-) embryos develop an abnormally branched aortic plexus with a markedly narrowed avascular midline. In vitro cultures and avian grafting experiments show strong repulsion of ECs by Sema3E-expressing cells. We further identify the mouse notochord as a rich source of multiple redundant neuronal guidance cues. Mouse embryos that lack notochords fail to form cohesive aortic vessels because of loss of the avascular midline, yet maintain lateral avascular zones. We demonstrate that lateral avascular zones are directly generated by the lateral plate mesoderm, a critical source of Sema3E.

conclusionsThese findings demonstrate that Sema3E-generated avascular zones are critical regulators of mammalian cardiovascular patterning and are the first to identify a repulsive role for the lateral plate mesoderm. Integration of multiple, and in some cases redundant, repulsive cues from various tissues is critical to patterning the first embryonic blood vessels.

Indexed as

AnimalsAortaBlood VesselsCells, CulturedCytoskeletal ProteinsEmbryo, MammalianEndothelium, VascularForkhead Transcription FactorsGlycoproteinsHepatocyte Nuclear Factor 3-betaIn Vitro TechniquesMembrane ProteinsMesodermMiceMice, KnockoutModels, AnimalCytoskeletal ProteinsForkhead Transcription FactorsFoxa2 protein, mouseFoxh1 protein, mouseGlycoproteinsHepatocyte Nuclear Factor 3-betaMembrane ProteinsSema3e protein, mouseSemaphorins

Identifiers

PMID22076636
PMCPMC3253216
OpenAlexW2163409186

What OpenQuestion holds

Textmetadata
LicenceTDM
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.