Evidence map›Paper›PMID 26443636›Full record

ArticleDevelopment (Cambridge, England)2015

Wnt/β-catenin signaling modulates corneal epithelium stratification via inhibition of Bmp4 during mouse development.

Yujin Zhang, Lung-Kun Yeh, Suohui Zhang, Mindy Call, Yong Yuan, Mayu Yasunaga, Winston W-Y Kao, Chia-Yang Liu

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Development (Cambridge, England), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed
2.9field-weighted citation impact, top 9% 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

44 citing papers in PubMed, 129 citations in OpenAlex.

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  12. Effects of bone morphogenetic proteins on epithelial repair.Experimental biology and medicine (Maywood, N.J.) · 2021
    Review
  13. Article
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  15. Article
  16. Review
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  18. Article
  19. Regulation of bone morphogenetic protein 4 on epithelial tissue.Journal of cell communication and signaling · 2020
    Review
  20. 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

8 authors at 4 institutions in 3 countries.

Yujin ZhangEdith J. Crawley Vision Research Center, Department of Ophthalmology, University of Cincinnati School of Medicine, Cincinnati, OH 45267, USA School of Optometry, Indiana University, Bloomington, IN 47405, USA zhang512@iu.edu liuchia@iu.edu.
Lung-Kun YehDepartment of Ophthalmology, Chang-Gung Memorial Hospital, Linkou, Taoyuan 333, Taiwan, R.O.C Chang-Gung University College of Medicine, Taoyuan 33302, Taiwan, R.O.C.
Suohui ZhangEdith J. Crawley Vision Research Center, Department of Ophthalmology, University of Cincinnati School of Medicine, Cincinnati, OH 45267, USA Undergraduate Programs of Biology, Ohio State University, Columbus, OH 43210, USA.
Mindy CallEdith J. Crawley Vision Research Center, Department of Ophthalmology, University of Cincinnati School of Medicine, Cincinnati, OH 45267, USA.
Yong YuanEdith J. Crawley Vision Research Center, Department of Ophthalmology, University of Cincinnati School of Medicine, Cincinnati, OH 45267, USA.
Mayu YasunagaHealth Research Institute, National Institute of Advanced Industrial Science and Technology, Takamatsu 761-0395, Japan.
Winston W-Y KaoEdith J. Crawley Vision Research Center, Department of Ophthalmology, University of Cincinnati School of Medicine, Cincinnati, OH 45267, USA.
Chia-Yang LiuEdith J. Crawley Vision Research Center, Department of Ophthalmology, University of Cincinnati School of Medicine, Cincinnati, OH 45267, USA School of Optometry, Indiana University, Bloomington, IN 47405, USA zhang512@iu.edu liuchia@iu.edu.
University of Cincinnati · USChang Gung University · TWNational Institute of Advanced Industrial Science and Technology · JPThe Ohio State University · US

Funding

Roles of Growth Factors on Corneal MorphogenesisR01EY013755 · NEI · UNIVERSITY OF CINCINNATI · PI KAO, WINSTON W · 2002 to 2013
$4.0M
Molecular mechanism of corneal epithelial stratification and innervationR01EY029071 · NEI · UNIVERSITY OF CINCINNATI · PI LIU, CHIA-YANG · 2019 to 2022
$2.1M
Mouse Model for Eyelid Disease: Congenital BlepharophimosisR01EY021501 · NEI · UNIVERSITY OF CINCINNATI · PI LIU, CHIA-YANG · 2011 to 2015
$1.9M
New Insights into the Ocular Surface in Health and DiseaseR01EY023680 · NEI · TRUSTEES OF INDIANA UNIVERSITY · PI LIU, CHIA-YANG · 2015 to 2017
$1.3M
NEI NIH HHS EY13755NEI NIH HHS R01 EY013755NEI NIH HHS R01 EY021501NEI NIH HHS R01 EY023680NEI NIH HHS R01 EY029071NEI NIH HHS R01 EY21501
6 · The paper itself

Abstract

The development of organs with an epithelial parenchyma relies on reciprocal mesenchymal-epithelial communication. Mouse corneal epithelium stratification is the consequence of a coordinated developmental process based on mesenchymal-epithelial interactions. The molecular mechanism underlying these interactions remains unclear. The Wnt/β-catenin signaling pathway is involved in fundamental aspects of development through the regulation of various growth factors. Here, we show that conditional ablation of either β-catenin (Ctnnb1(cKO)) or co-receptors Lrp5/6 (Lrp5/6(cKO)) in corneal stromal cells results in precocious stratification of the corneal epithelium. By contrast, ectopic expression of a murine Ctnnb1 gain-of-function mutant (Ctnnb1(cGOF)) retards corneal epithelium stratification. We also discovered that Bmp4 is upregulated in the absence of β-catenin in keratocytes, which further triggers ERK1/2 (Mapk3/1) and Smad1/5 phosphorylation and enhances transcription factor p63 (Trp63) expression in mouse corneal basal epithelial cells and in a human corneal epithelial cell line (HTCE). Interestingly, mouse neonates given a subconjunctival BMP4 injection displayed a phenotype resembling that of Ctnnb1(cKO). Conditional ablation of Bmp4 eradicates the phenotype produced in Ctnnb1(cKO) mice. Furthermore, ChIP and promoter-luciferase assays show that β-catenin binds to and suppresses Bmp4 promoter activity. These data support the concept that cross-talk between the Wnt/β-catenin/Bmp4 axis (in the stromal mesenchyme) and Bmp4/p63 signaling (in the epithelium) plays a pivotal role in epithelial stratification during corneal morphogenesis.

Indexed as

Animalsbeta CateninBlotting, WesternBone Morphogenetic Protein 4Chromatin ImmunoprecipitationDoxycyclineEpithelium, CornealFluorescenceGalactosidesGene Expression Regulation, DevelopmentalHistological TechniquesImmunohistochemistryIndolesLow Density Lipoprotein Receptor-Related Protein-5Low Density Lipoprotein Receptor-Related Protein-6Luciferases5-bromo-4-chloro-3-indolyl beta-galactosidebeta CateninBmp4 protein, mouseBone Morphogenetic Protein 4CTNNB1 protein, mouseDoxycyclineGalactosidesIndolesLow Density Lipoprotein Receptor-Related Protein-5Low Density Lipoprotein Receptor-Related Protein-6Lrp5 protein, mouseLrp6 protein, mouseLuciferasesPhosphoproteinsTrans-ActivatorsTrp63 protein, mouseBmp4Mesenchymal-epithelial interactionsMouseOcular surfacePrecocious epithelium stratificationWnt/β-catenin signaling

Identifiers

PMID26443636
PMCPMC4631757
OpenAlexW2414555491

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.