Evidence map›Paper›PMID 34487959›Full record

ArticleBiochemical and biophysical research communications2021

Noncanonical Notch signals have opposing roles during cardiac development.

Matthew Miyamoto, Peter Andersen, Edrick Sulistio, Xihe Liu, Sean Murphy, Suraj Kannan, Lucy Nam, William Miyamoto, Emmanouil Tampakakis, Narutoshi Hibino and 2 more

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

Article in Biochemical and biophysical research communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.3field-weighted citation impact, top 43% 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

5 citing papers in PubMed, 7 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. The molecular mechanisms of cardiac development and related diseases.Signal transduction and targeted therapy · 2024
    Review
  5. 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

12 authors at 3 institutions in 2 countries.

Matthew MiyamotoDivision of Cardiology, Department of Medicine, Johns Hopkins University, Baltimore, MD, USA; Heart and Vascular Institute, Cellular and Molecular Medicine, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Biomedical Engineering, Department of Cell Biology, Johns Hopkins University, Baltimore, MD, USA.
Peter AndersenDivision of Cardiology, Department of Medicine, Johns Hopkins University, Baltimore, MD, USA; Heart and Vascular Institute, Cellular and Molecular Medicine, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Biomedical Engineering, Department of Cell Biology, Johns Hopkins University, Baltimore, MD, USA.
Edrick SulistioDivision of Cardiology, Department of Medicine, Johns Hopkins University, Baltimore, MD, USA; Heart and Vascular Institute, Cellular and Molecular Medicine, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Biomedical Engineering, Department of Cell Biology, Johns Hopkins University, Baltimore, MD, USA.
Xihe LiuDivision of Cardiology, Department of Medicine, Johns Hopkins University, Baltimore, MD, USA; Heart and Vascular Institute, Cellular and Molecular Medicine, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Biomedical Engineering, Department of Cell Biology, Johns Hopkins University, Baltimore, MD, USA.
Sean MurphyDivision of Cardiology, Department of Medicine, Johns Hopkins University, Baltimore, MD, USA; Heart and Vascular Institute, Cellular and Molecular Medicine, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Biomedical Engineering, Department of Cell Biology, Johns Hopkins University, Baltimore, MD, USA.
Suraj KannanDivision of Cardiology, Department of Medicine, Johns Hopkins University, Baltimore, MD, USA; Heart and Vascular Institute, Cellular and Molecular Medicine, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Biomedical Engineering, Department of Cell Biology, Johns Hopkins University, Baltimore, MD, USA.
Lucy NamDivision of Cardiology, Department of Medicine, Johns Hopkins University, Baltimore, MD, USA; Heart and Vascular Institute, Cellular and Molecular Medicine, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Biomedical Engineering, Department of Cell Biology, Johns Hopkins University, Baltimore, MD, USA; Department of Surgery, Massachusetts General Hospital, Boston, MA.
William MiyamotoDivision of Cardiology, Department of Medicine, Johns Hopkins University, Baltimore, MD, USA; Heart and Vascular Institute, Cellular and Molecular Medicine, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Biomedical Engineering, Department of Cell Biology, Johns Hopkins University, Baltimore, MD, USA.
Emmanouil TampakakisDivision of Cardiology, Department of Medicine, Johns Hopkins University, Baltimore, MD, USA; Heart and Vascular Institute, Cellular and Molecular Medicine, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Narutoshi HibinoDepartment of Surgery, The University of Chicago Medical Center, Chicago, IL, USA.
Hideki UosakiDivision of Regenerative Medicine, Center for Molecular Medicine, Jichi Medical University, Shimotsuke, Tochigi, Japan.
Chulan KwonDivision of Cardiology, Department of Medicine, Johns Hopkins University, Baltimore, MD, USA; Heart and Vascular Institute, Cellular and Molecular Medicine, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Biomedical Engineering, Department of Cell Biology, Johns Hopkins University, Baltimore, MD, USA. Electronic address: ckwon13@jhmi.edu.
Johns Hopkins University · USJichi Medical University · JPUniversity of Chicago Medical Center · US

Funding

PATHOPHYSIOLOGY OF MYOCARDIAL DISEASEST32HL007227 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI Chulan Kwon, WENDY S POST · 1985 to 2026
$21.2M
Medical Scientist Training ProgramT32GM136577 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI ANDREA L COX · 2020 to 2026
$13.4M
BIOMEDICAL ENGINEERING TRAINING PROGRAMT32GM007057 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI KANOLD, PATRICK O, KARCHIN, RACHEL · 1985 to 2023
$10.4M
Non-Canonical Notch Regulation of Cardiovascular ProgenitorsR01HL111198 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI KWON, CHULAN · 2012 to 2016
$2.0M
Regulation of Cardiac Progenitor MaintenanceR01HD086026 · NICHD · JOHNS HOPKINS UNIVERSITY · PI KWON, CHULAN · 2016 to 2020
$1.6M
Engineering a power switch to study the contribution of stem cell-derived cardiomyocytes on heart regenerationK08HL145135 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI TAMPAKAKIS, EMMANOUIL · 2019 to 2023
$859k
American Heart Association-American Stroke Association 15GRNT25700066American Heart Association-American Stroke Association 17GRNT33670432American Heart Association-American Stroke Association 18EIA33890038NHLBI NIH HHS K08 HL145135NHLBI NIH HHS R01 HL111198NHLBI NIH HHS T32 HL007227NICHD NIH HHS R01 HD086026NIGMS NIH HHS T32 GM007057NIGMS NIH HHS T32 GM136577
6 · The paper itself

Abstract

The Notch pathway is an ancient intercellular signaling system with crucial roles in numerous cell-fate decision processes across species. While the canonical pathway is activated by ligand-induced cleavage and nuclear localization of membrane-bound Notch, Notch can also exert its activity in a ligand/transcription-independent fashion, which is conserved in Drosophila, Xenopus, and mammals. However, the noncanonical role remains poorly understood in in vivo processes. Here we show that increased levels of the Notch intracellular domain (NICD) in the early mesoderm inhibit heart development, potentially through impaired induction of the second heart field (SHF), independently of the transcriptional effector RBP-J. Similarly, inhibiting Notch cleavage, shown to increase noncanonical Notch activity, suppressed SHF induction in embryonic stem cell (ESC)-derived mesodermal cells. In contrast, NICD overexpression in late cardiac progenitor cells lacking RBP-J resulted in an increase in heart size. Our study suggests that noncanonical Notch signaling has stage-specific roles during cardiac development.

Indexed as

Signal TransductionAnimalsCell DifferentiationCells, CulturedGATA4 Transcription FactorHeartHomeobox Protein Nkx-2.5Homeodomain ProteinsImmunoglobulin J Recombination Signal Sequence-Binding ProteinMesodermMiceMice, KnockoutMice, TransgenicMouse Embryonic Stem CellsMyocardiumReceptors, NotchGata4 protein, mouseGATA4 Transcription FactorHomeobox Protein Nkx-2.5Homeodomain ProteinsImmunoglobulin J Recombination Signal Sequence-Binding ProteinNkx2-5 protein, mouseRbpj protein, mouseReceptors, NotchSix2 protein, mouseT-Box Domain ProteinsTbx1 protein, mouseTranscription FactorsHeart developmentNoncanonical Notch signalingNotch signalingSecond heart field

Identifiers

PMID34487959
PMCPMC8484041
OpenAlexW3198850550

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.