Back to Search
Start Over
Wnt/β-catenin signaling modulates corneal epithelium stratification via inhibition of Bmp4 during mouse development
- Source :
- Development. 142:3383-3393
- Publication Year :
- 2015
- Publisher :
- The Company of Biologists, 2015.
-
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 (Ctnnb1cKO) or co-receptors Lrp5/6 (Lrp5/6cKO) in corneal stromal cells results in precocious stratification of the corneal epithelium. By contrast, ectopic expression of a murine Ctnnb1 gain-of-function mutant (Ctnnb1cGOF) 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 Ctnnb1cKO. Conditional ablation of Bmp4 eradicates the phenotype produced in Ctnnb1cKO 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.
- Subjects :
- Chromatin Immunoprecipitation
Indoles
Beta-catenin
Stromal cell
Mesenchyme
Blotting, Western
Bone Morphogenetic Protein 4
Real-Time Polymerase Chain Reaction
Fluorescence
Mice
Microscopy, Electron, Transmission
Morphogenesis
medicine
Animals
Luciferases
Wnt Signaling Pathway
Molecular Biology
Research Articles
beta Catenin
Corneal epithelium
Mice, Knockout
biology
Histological Techniques
Epithelium, Corneal
Wnt signaling pathway
Gene Expression Regulation, Developmental
Galactosides
LRP5
Phosphoproteins
Immunohistochemistry
Molecular biology
Epithelium
Cell biology
Low Density Lipoprotein Receptor-Related Protein-5
medicine.anatomical_structure
Doxycycline
Low Density Lipoprotein Receptor-Related Protein-6
Trans-Activators
biology.protein
Ectopic expression
Developmental Biology
Subjects
Details
- ISSN :
- 14779129 and 09501991
- Volume :
- 142
- Database :
- OpenAIRE
- Journal :
- Development
- Accession number :
- edsair.doi.dedup.....351bc232c5c02df7a29904877d9c53bf