Evidence map›Paper›PMID 41309607›Full record

ArticleNature communications2025

Convergent flow-mediated mesenchymal force drives embryonic foregut constriction and splitting.

Rui Yan, Ludwig A Hoffmann, Panagiotis Oikonomou, Deng Li, ChangHee Lee, Hasreet K Gill, Alessandro Mongera, Nandan L Nerurkar, L Mahadevan, Clifford J Tabin

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
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

4 citing papers in PubMed.

  1. Mechanics of compression-driven morphogenesis.Development (Cambridge, England) · 2026
    Review
  2. Article
  3. Article
  4. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors.

Rui YanDepartment of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0003-3391-133X
Ludwig A HoffmannSchool of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-3674-9043
Panagiotis OikonomouDepartment of Biomedical Engineering, Columbia University, New York, NY, USA.ORCID http://orcid.org/0000-0002-6312-361X
Deng LiDepartment of Bioengineering, Northeastern University, Boston, MA, USA.ORCID http://orcid.org/0009-0002-3030-8009
ChangHee LeeDepartment of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
Hasreet K GillDepartment of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
Alessandro MongeraDepartment of Cell & Developmental Biology, University College London, London, UK.ORCID http://orcid.org/0000-0001-9344-9808
Nandan L NerurkarDepartment of Biomedical Engineering, Columbia University, New York, NY, USA.ORCID http://orcid.org/0000-0003-1309-8919
L MahadevanSchool of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA. lmahadev@g.harvard.edu.ORCID http://orcid.org/0000-0002-5114-0519
Clifford J TabinDepartment of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, USA. tabin@genetics.med.harvard.edu.ORCID http://orcid.org/0000-0002-2957-4871

Funding

Signals and mechanical forces controlling radial gut morphogenesisR01HD087234 · NICHD · HARVARD MEDICAL SCHOOL · PI TABIN, CLIFFORD J. · 2016 to 2025
$3.2M
NICHD NIH HHS R01 HD087234U.S. Department of Health & Human Services | NIH | Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) HD087234
6 · The paper itself

Abstract

The transformation of a two-dimensional epithelial sheet into various three-dimensional structures is a critical process in generating the diversity of animal forms. Previous studies of epithelial folding have revealed diverse mechanisms driven by epithelium-intrinsic or -extrinsic forces. Yet little is known about the biomechanical basis of epithelial splitting, which involves extreme folding and eventually a topological transition breaking the epithelial tube. Here, we leverage tracheal-esophageal separation (TES), a critical and highly conserved morphogenetic event during tetrapod embryogenesis, as a model system for interrogating epithelial tube splitting. We identify an evolutionarily conserved, compressive force exerted by the mesenchyme surrounding the epithelium, as being necessary to drive epithelial constriction and splitting. The compressive force is mediated by localized convergent flow of mesenchymal cells towards the epithelium. Sonic hedgehog (SHH) secreted by the epithelium functions as an attractive cue for mesenchymal cells. Removal of the mesenchyme, inhibition of cell migration, or loss of SHH signaling all abrogate TES, which can be rescued by externally applied pressure. These results unveil the biomechanical basis of epithelial splitting and suggest plausible mesenchymal origins of tracheal-esophageal birth defects.

Indexed as

EsophagusMesodermTracheaAnimalsBiomechanical PhenomenaCell MovementEmbryonic DevelopmentEpitheliumHedgehog ProteinsMiceMorphogenesisSignal TransductionHedgehog Proteins

Identifiers

PMID41309607
PMCPMC12660939

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.