Evidence map›Paper›PMID 34737283›Full record

ArticleNature communications2021

Smad4 controls signaling robustness and morphogenesis by differentially contributing to the Nodal and BMP pathways.

Luca Guglielmi, Claire Heliot, Sunil Kumar, Yuriy Alexandrov, Ilaria Gori, Foteini Papaleonidopoulou, Christopher Barrington, Philip East, Andrew D Economou, Paul M W French and 2 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
2.8field-weighted citation impact, top 8% 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

15 citing papers in PubMed, 48 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Coupling of stemness maintenance with cell cycle control in stem cells.Frontiers in cell and developmental biology · 2025
    Review
  6. Review
  7. Article
  8. Article
  9. Review
  10. Article
  11. Context-dependent TGFβ family signalling in cell fate regulation.Nature reviews. Molecular cell biology · 2023
    Review
  12. Article
  13. Article
  14. Article
  15. 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 2 institutions in 1 country.

Luca GuglielmiDevelopmental Signalling Laboratory, The Francis Crick Institute, London, NW1 1AT, UK.
Claire HeliotDevelopmental Signalling Laboratory, The Francis Crick Institute, London, NW1 1AT, UK.
Sunil KumarAdvanced Light Microscopy, The Francis Crick Institute, London, NW1 1AT, UK.ORCID 0000-0001-8200-9671
Yuriy AlexandrovAdvanced Light Microscopy, The Francis Crick Institute, London, NW1 1AT, UK.
Ilaria GoriDevelopmental Signalling Laboratory, The Francis Crick Institute, London, NW1 1AT, UK.
Foteini PapaleonidopoulouDevelopmental Signalling Laboratory, The Francis Crick Institute, London, NW1 1AT, UK.ORCID 0000-0001-9955-9477
Christopher BarringtonBioinformatics and Biostatistics Facility, The Francis Crick Institute, London, NW1 1AT, UK.ORCID 0000-0003-1281-2658
Philip EastBioinformatics and Biostatistics Facility, The Francis Crick Institute, London, NW1 1AT, UK.ORCID 0000-0001-5801-5713
Andrew D EconomouDevelopmental Signalling Laboratory, The Francis Crick Institute, London, NW1 1AT, UK.
Paul M W FrenchDepartment of Physics, Imperial College London, SW7 2AZ, London, UK.
James McGintyDepartment of Physics, Imperial College London, SW7 2AZ, London, UK.
Caroline S HillDevelopmental Signalling Laboratory, The Francis Crick Institute, London, NW1 1AT, UK. caroline.hill@crick.ac.uk.ORCID 0000-0002-8632-0480
The Francis Crick Institute · GBImperial College London · GB

Funding

Cancer Research UK 15681Medical Research CouncilWellcome Trust FC001095
6 · The paper itself

Abstract

The transcriptional effector SMAD4 is a core component of the TGF-β family signaling pathways. However, its role in vertebrate embryo development remains unresolved. To address this, we deleted Smad4 in zebrafish and investigated the consequences of this on signaling by the TGF-β family morphogens, BMPs and Nodal. We demonstrate that in the absence of Smad4, dorsal/ventral embryo patterning is disrupted due to the loss of BMP signaling. However, unexpectedly, Nodal signaling is maintained, but lacks robustness. This Smad4-independent Nodal signaling is sufficient for mesoderm specification, but not for optimal endoderm specification. Furthermore, using Optical Projection Tomography in combination with 3D embryo morphometry, we have generated a BMP morphospace and demonstrate that Smad4 mutants are morphologically indistinguishable from embryos in which BMP signaling has been genetically/pharmacologically perturbed. Smad4 is thus differentially required for signaling by different TGF-β family ligands, which has implications for diseases where Smad4 is mutated or deleted.

Indexed as

AnimalsBone Morphogenetic ProteinsEmbryonic DevelopmentEndodermGene Knockout TechniquesMesodermMorphogenesisNodal ProteinSignal TransductionSmad4 ProteinTransforming Growth Factor betaZebrafishZebrafish ProteinsBone Morphogenetic ProteinsNodal Proteinsmad4a protein, zebrafishSmad4 ProteinTransforming Growth Factor betaZebrafish Proteins

Identifiers

PMID34737283
PMCPMC8569018
OpenAlexW3208566152

What Socratic holds

Textmetadata
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 Socratic graph.