Evidence map›Paper›PMID 26863187›Full record

ArticleNature2016

Visualization of a short-range Wnt gradient in the intestinal stem-cell niche.

Henner F Farin, Ingrid Jordens, Mohammed H Mosa, Onur Basak, Jeroen Korving, Daniele V F Tauriello, Karin de Punder, Stephane Angers, Peter J Peters, Madelon M Maurice and 1 more

Abstract read
PubMed Publisher
In one paragraph

Article in Nature, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 306 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
306citing papers in PubMed, 1 pooled it
40.6field-weighted citation impact, top 1% 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

306 citing papers in PubMed, 1 synthesis or guideline pooled it, 521 citations in OpenAlex.

  1. Pooled it
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  6. Biophysics of lumen morphogenesis.Development (Cambridge, England) · 2026
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246 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 4 institutions in 3 countries.

Henner F FarinHubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and University Medical Center Utrecht, 3584CT Utrecht, the Netherlands.
Ingrid JordensDepartment of Cell Biology, Center for Molecular Medicine, University Medical Center Utrecht, 3584CX Utrecht, the Netherlands.
Mohammed H MosaGerman Cancer Consortium (DKTK), 69120 Heidelberg, Germany.
Onur BasakHubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and University Medical Center Utrecht, 3584CT Utrecht, the Netherlands.
Jeroen KorvingHubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and University Medical Center Utrecht, 3584CT Utrecht, the Netherlands.
Daniele V F TaurielloDepartment of Cell Biology, Center for Molecular Medicine, University Medical Center Utrecht, 3584CX Utrecht, the Netherlands.
Karin de PunderThe Maastricht Multimodal Molecular Imaging institute, Maastricht University, 6229ER Maastricht, the Netherlands.
Stephane AngersLeslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario M5S 3M2, Canada.
Peter J PetersThe Maastricht Multimodal Molecular Imaging institute, Maastricht University, 6229ER Maastricht, the Netherlands.
Madelon M MauriceDepartment of Cell Biology, Center for Molecular Medicine, University Medical Center Utrecht, 3584CX Utrecht, the Netherlands.
Hans CleversHubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and University Medical Center Utrecht, 3584CT Utrecht, the Netherlands.
University Medical Center Utrecht · NLDeutschen Konsortium für Translationale Krebsforschung · DEMaastricht University · NLUniversity of Toronto · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Mammalian Wnt proteins are believed to act as short-range signals, yet have not been previously visualized in vivo. Self-renewal, proliferation and differentiation are coordinated along a putative Wnt gradient in the intestinal crypt. Wnt3 is produced specifically by Paneth cells. Here we have generated an epitope-tagged, functional Wnt3 knock-in allele. Wnt3 covers basolateral membranes of neighbouring stem cells. In intestinal organoids, Wnt3-transfer involves direct contact between Paneth cells and stem cells. Plasma membrane localization requires surface expression of Frizzled receptors, which in turn is regulated by the transmembrane E3 ligases Rnf43/Znrf3 and their antagonists Lgr4-5/R-spondin. By manipulating Wnt3 secretion and by arresting stem-cell proliferation, we demonstrate that Wnt3 mainly travels away from its source in a cell-bound manner through cell division, and not through diffusion. We conclude that stem-cell membranes constitute a reservoir for Wnt proteins, while Frizzled receptor turnover and 'plasma membrane dilution' through cell division shape the epithelial Wnt3 gradient.

Indexed as

Stem Cell NicheWnt Signaling PathwayAllelesAnimalsCell AdhesionCell DivisionCell MembraneDiffusionFemaleFrizzled ReceptorsGene Knock-In TechniquesIntercellular Signaling Peptides and ProteinsIntestinal MucosaMaleMiceOrganoidsFrizzled ReceptorsIntercellular Signaling Peptides and ProteinsLGR4 protein, mouseReceptors, G-Protein-CoupledRNF43 protein, mouseUbiquitin-Protein LigasesWnt3 ProteinWnt3 protein, mouseZnrf3 protein, mouse

Identifiers

PMID26863187
OpenAlexW2258083311

What OpenQuestion holds

Textmetadata
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.