Evidence map›Paper›PMID 34133940›Full record

ArticleCell2021

Budding epithelial morphogenesis driven by cell-matrix versus cell-cell adhesion.

Shaohe Wang, Kazue Matsumoto, Samantha R Lish, Alexander X Cartagena-Rivera, Kenneth M Yamada

Open access · bronzeAbstract read
In one paragraph

Article in Cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.

0numbers the graph read from it
0cells of the map it votes in
74citing papers in PubMed
7.7field-weighted citation impact, top 2% 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

74 citing papers in PubMed, 119 citations in OpenAlex.

  1. Article
  2. Prepatterned Tissue Stiffness Gradient Controls Organ shape and size.bioRxiv : the preprint server for biology · 2026
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  17. Article
  18. Review
  19. The Mechanics of Building Functional Organs.Cold Spring Harbor perspectives in biology · 2025
    Review
  20. Review

14 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

5 authors at 2 institutions in 1 country.

Shaohe WangCell Biology Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA. Electronic address: shaohe.wang@nih.gov.
Kazue MatsumotoCell Biology Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
Samantha R LishSection on Mechanobiology, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD, USA.
Alexander X Cartagena-RiveraSection on Mechanobiology, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD, USA.
Kenneth M YamadaCell Biology Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA. Electronic address: kenneth.yamada@nih.gov.
National Institutes of Health · USNational Institute of Dental and Craniofacial Research · US

Funding

Craniofacial Developmental DynamicsZIADE000525 · NIDCR · NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH · PI YAMADA, KENNETH · 2009 to 2025
$14.5M
Cell-Matrix Interactions and MigrationZIADE000524 · NIDCR · NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH · PI YAMADA, KENNETH · 2009 to 2025
$10.2M
MechanobiologyZIAEB000094 · NIBIB · NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING · PI CARTAGENA-RIVERA, ALEXANDER · 2020 to 2025
$6.0M
REGULATION OF CELL ADHESION, MIGRATION, AND MORPHOGENESISZ01DE000525 · NIDCR · NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH · PI YAMADA, KENNETH MANAO · 1991 to 2008
$1.5M
Intramural NIH HHS Z01 DE000525Intramural NIH HHS ZIA DE000525Intramural NIH HHS ZIA EB000094
6 · The paper itself

Abstract

Many embryonic organs undergo epithelial morphogenesis to form tree-like hierarchical structures. However, it remains unclear what drives the budding and branching of stratified epithelia, such as in the embryonic salivary gland and pancreas. Here, we performed live-organ imaging of mouse embryonic salivary glands at single-cell resolution to reveal that budding morphogenesis is driven by expansion and folding of a distinct epithelial surface cell sheet characterized by strong cell-matrix adhesions and weak cell-cell adhesions. Profiling of single-cell transcriptomes of this epithelium revealed spatial patterns of transcription underlying these cell adhesion differences. We then synthetically reconstituted budding morphogenesis by experimentally suppressing E-cadherin expression and inducing basement membrane formation in 3D spheroid cultures of engineered cells, which required β1-integrin-mediated cell-matrix adhesion for successful budding. Thus, stratified epithelial budding, the key first step of branching morphogenesis, is driven by an overall combination of strong cell-matrix adhesion and weak cell-cell adhesion by peripheral epithelial cells.

Indexed as

MorphogenesisAnimalsBasement MembraneCell AdhesionCell DivisionCell-Matrix JunctionsCell MovementCell TrackingEmbryo, MammalianEpithelial CellsEpitheliumGene Expression Regulation, DevelopmentalHEK293 CellsHumansIntegrinsMiceIntegrinsbranching morphogenesisbudding morphogenesiscell-cell adhesioncell-matrix adhesiondifferential adhesionE-cadherinepithelial morphogenesisintegrinsalivary glandtissue engineering

Identifiers

PMID34133940
PMCPMC8287763
OpenAlexW3167390221

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.