Evidence map›Paper›PMID 33483469›Full record

ArticleCell death & disease2021

The Hippo pathway component Wwc2 is a key regulator of embryonic development and angiogenesis in mice.

Anke Hermann, Guangming Wu, Pavel I Nedvetsky, Viktoria C Brücher, Charlotte Egbring, Jakob Bonse, Verena Höffken, Dirk Oliver Wennmann, Matthias Marks, Michael P Krahn and 4 more

Open access · goldAbstract read
In one paragraph

Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
2.1field-weighted citation impact, top 14% 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

21 citing papers in PubMed, 29 citations in OpenAlex.

  1. Widefield optical coherence tomography angiography of fellow eyes in patients with Coats Disease.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2026
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  14. WWC2 modulates GABACell reports · 2024
    Article
  15. Review
  16. Association analysis of polymorphisms inFrontiers in genetics · 2024
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  20. Lack of WWC2 Protein Leads to Aberrant Angiogenesis in Postnatal Mice.International journal of molecular sciences · 2021
    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

14 authors at 3 institutions in 2 countries.

Anke Hermann *Department of Nephrology, Hypertension and Rheumatology, University Hospital Münster, Münster, Germany.
Guangming Wu *Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, P. R. China.
Pavel I NedvetskyDepartment of Nephrology, Hypertension and Rheumatology, University Hospital Münster, Münster, Germany.
Viktoria C BrücherDepartment of Ophthalmology, University Hospital Münster, Münster, Germany.
Charlotte EgbringDepartment of Ophthalmology, University Hospital Münster, Münster, Germany.
Jakob BonseDepartment of Nephrology, Hypertension and Rheumatology, University Hospital Münster, Münster, Germany.
Verena HöffkenDepartment of Nephrology, Hypertension and Rheumatology, University Hospital Münster, Münster, Germany.
Dirk Oliver WennmannDepartment of Nephrology, Hypertension and Rheumatology, University Hospital Münster, Münster, Germany.
Matthias MarksDepartment of Neurobiological Research, University Aachen, Aachen, Germany.
Michael P KrahnDepartment of Nephrology, Hypertension and Rheumatology, University Hospital Münster, Münster, Germany.ORCID http://orcid.org/0000-0001-7718-9890
Hans SchölerMedical Faculty, University Münster, Münster, Germany.
Peter HeiduschkaDepartment of Ophthalmology, University Hospital Münster, Münster, Germany.
Hermann PavenstädtDepartment of Nephrology, Hypertension and Rheumatology, University Hospital Münster, Münster, Germany.
Joachim KremerskothenDepartment of Nephrology, Hypertension and Rheumatology, University Hospital Münster, Münster, Germany. kremers@uni-muenster.de.
University Hospital Münster · DEGuangzhou Regenerative Medicine and Health Guangdong Laboratory · CNRWTH Aachen University · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The WW-and-C2-domain-containing (WWC) protein family is involved in the regulation of cell differentiation, cell proliferation, and organ growth control. As upstream components of the Hippo signaling pathway, WWC proteins activate the Large tumor suppressor (LATS) kinase that in turn phosphorylates Yes-associated protein (YAP) and its paralog Transcriptional coactivator-with-PDZ-binding motif (TAZ) preventing their nuclear import and transcriptional activity. Inhibition of WWC expression leads to downregulation of the Hippo pathway, increased expression of YAP/TAZ target genes and enhanced organ growth. In mice, a ubiquitous Wwc1 knockout (KO) induces a mild neurological phenotype with no impact on embryogenesis or organ growth. In contrast, we could show here that ubiquitous deletion of Wwc2 in mice leads to early embryonic lethality. Wwc2 KO embryos display growth retardation, a disturbed placenta development, impaired vascularization, and finally embryonic death. A whole-transcriptome analysis of embryos lacking Wwc2 revealed a massive deregulation of gene expression with impact on cell fate determination, cell metabolism, and angiogenesis. Consequently, a perinatal, endothelial-specific Wwc2 KO in mice led to disturbed vessel formation and vascular hypersprouting in the retina. In summary, our data elucidate a novel role for Wwc2 as a key regulator in early embryonic development and sprouting angiogenesis in mice.

Indexed as

Adaptor Proteins, Signal TransducingAnimalsCell DifferentiationEmbryonic DevelopmentFemaleHippo Signaling PathwayMaleMiceMice, KnockoutNeovascularization, PhysiologicProtein Serine-Threonine KinasesSignal TransductionAdaptor Proteins, Signal TransducingProtein Serine-Threonine Kinases

Identifiers

PMID33483469
PMCPMC7822818
OpenAlexW3122358577

What OpenQuestion holds

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LicenceCC BY
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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.