Evidence map›Paper›PMID 28446132›Full record

ArticleBMC developmental biology2017

Pcsk5 is required in the early cranio-cardiac mesoderm for heart development.

Dorota Szumska, Milena Cioroch, Angela Keeling, Annik Prat, Nabil G Seidah, Shoumo Bhattacharya

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in BMC developmental biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.6field-weighted citation impact, top 34% 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

7 citing papers in PubMed, 12 citations in OpenAlex.

  1. Article
  2. Article
  3. Mouse embryo phenotyping using X-ray microCT.Frontiers in cell and developmental biology · 2022
    Review
  4. Article
  5. Review
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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

6 authors at 3 institutions in 2 countries.

Dorota SzumskaDivision of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, the Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford, OX3 7BN, UK.
Milena CiorochDivision of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, the Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford, OX3 7BN, UK.
Angela KeelingDivision of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, the Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford, OX3 7BN, UK.
Annik PratLaboratory of Biochemical Neuroendocrinology, Montreal Clinical Research Institute (IRCM), 110 Pine Ave west, Montreal, QC, H2W1R7, Canada.
Nabil G SeidahLaboratory of Biochemical Neuroendocrinology, Montreal Clinical Research Institute (IRCM), 110 Pine Ave west, Montreal, QC, H2W1R7, Canada.
Shoumo BhattacharyaDivision of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, the Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford, OX3 7BN, UK. sbhattac@well.ox.ac.uk.
Centre for Human Genetics · GBMontreal Clinical Research Institute · CAUniversity of Oxford · GB

Funding

INCREASED OXYGEN CONSUMPTION AND MYOCARDIAL STUNNINGF32HL008045 · NHLBI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI PATH, GREGORY J · 1989 to 1990
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British Heart Foundation PG/08/045/25069British Heart Foundation RG/10/17/28553
6 · The paper itself

Abstract

backgroundLoss of proprotein convertase subtilisin/kexin type 5 (Pcsk5) results in multiple developmental anomalies including cardiac malformations, caudal regression, pre-sacral mass, renal agenesis, anteroposterior patterning defects, and tracheo-oesophageal and anorectal malformations, and is a model for VACTERL/caudal regression/Currarino syndromes (VACTERL association - Vertebral anomalies, Anal atresia, Cardiac defects, Tracheoesophageal fistula and/or Esophageal atresia, Renal & Radial anomalies and Limb defects).

resultsUsing magnetic resonance imaging (MRI), we examined heart development in mouse embryos with zygotic and cardiac specific deletion of Pcsk5. We show that conditional deletion of Pcsk5 in all epiblastic lineages recapitulates all developmental malformations except for tracheo-esophageal malformations. Using a conditional deletion strategy, we find that there is an essential and specific requirement for Pcsk5 in the cranio-cardiac mesoderm for cardiogenesis, but not for conotruncal septation or any other aspect of embryonic development. Surprisingly, deletion of Pcsk5 in cardiogenic or pharyngeal mesodermal progenitors that form later from the cranio-cardiac mesoderm does not affect heart development. Neither is Pcsk5 essential in the neural crest, which drives conotruncal septation.

conclusionsOur results suggest that Pcsk5 may have an essential and early role in the cranio-cardiac mesoderm for heart development. Alternatively, it is possible that Pcsk5 may still play a critical role in Nkx2.5-expressing cardiac progenitors, with persistence of mRNA or protein accounting for the lack of effect of deletion on heart development.

Indexed as

AnimalsGene Expression Regulation, DevelopmentalGene Knockout TechniquesHeartMesodermMiceMice, KnockoutMutationOrganogenesisProprotein Convertase 5propeptide convertase 5, mouseProprotein Convertase 5CardiogenesisConditional knock-outMousePcsk5

Identifiers

PMID28446132
PMCPMC5407003
OpenAlexW2607737783

What OpenQuestion holds

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LicenceCC BY
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.