Evidence map›Paper›PMID 25428115›Full record

ArticleDevelopmental dynamics : an official publication of the American Association of Anatomists2015

Persistent Noggin arrests cardiomyocyte morphogenesis and results in early in utero lethality.

Olga Simmons, Paige Snider, Jain Wang, Robert J Schwartz, Yiping Chen, Simon J Conway

Open access · bronzeAbstract read
In one paragraph

Article in Developmental dynamics : an official publication of the American Association of Anatomists, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.3field-weighted citation impact, top 42% 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

2 citing papers in PubMed, 5 citations in OpenAlex.

  1. Article
  2. 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

6 authors at 4 institutions in 1 country.

Olga SimmonsDevelopmental Biology and Neonatal Medicine Program, HB Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana.
Paige Snider
Jain Wang
Robert J Schwartz
Yiping Chen
Simon J Conway
Indiana University – Purdue University Indianapolis · USIndiana University School of MedicineTulane University · USUniversity of Houston · US

Funding

NEURAL-CREST RELATED HEART DEFECTSR01HL060714 · NHLBI · MEDICAL COLLEGE OF GEORGIA (MCG) · PI CONWAY, SIMON JAMES · 1998 to 2017
$4.7M
NHLBI NIH HHS HL60714NHLBI NIH HHS R01 HL060714
6 · The paper itself

Abstract

backgroundMultiple bone morphogenetic protein (BMP) genes are expressed in the developing heart from the initiation to late-differentiation stages, and play pivotal roles in cardiovascular development. In this study, we investigated the requirement of BMP activity in heart development by transgenic over-expression of extracellular BMP antagonist Noggin.

resultsUsing Nkx2.5-Cre to drive lineage-restricted Noggin within cardiomyocyte progenitors, we show persistent Noggin arrests cardiac development at the linear heart stage. This is coupled with a significantly reduced cell proliferation rate, subsequent cardiomyocyte programmed cell death and reduction of downstream intracellular pSMAD1/5/8 expression. Noggin mutants exhibit reduced heartbeat which likely results in subsequent fully penetrant in utero lethality. Significantly, confocal and electron micrographic examination revealed considerably fewer contractile elements, as well as a lack of maturation of actin-myosin microfilaments. Molecular analysis demonstrated that ectopic Noggin-expressing regions in the early heart's pacemaker region, failed to express the potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4 (Hcn4), resulting in an overall decrease in Hcn4 levels.

conclusionsCombined, our results reveal a novel role for BMP signaling in the progression of heart development from the tubular heart stage to the looped stage by means of regulation of proliferation and promotion of maturation of the in utero heart's contractile apparatus and pacemaker.

Indexed as

Carrier ProteinsFetal DeathGene Expression Regulation, DevelopmentalMyocytes, CardiacStem CellsAnimalsFemaleHyperpolarization-Activated Cyclic Nucleotide-Gated ChannelsMiceMice, TransgenicMyocardial ContractionNoggin ProteinPregnancyCarrier ProteinsHcn4 protein, mouseHyperpolarization-Activated Cyclic Nucleotide-Gated ChannelsNoggin ProteinBMPbradycardiacardiomyocytecongenital heart defectscontractile apparatusmouse embryoNogginproliferationtransgenic overexpression

Identifiers

PMID25428115
PMCPMC4344892
OpenAlexW1909091518

What OpenQuestion holds

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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.