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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Zhang, Yujin Yeh, Lung-Kun Zhang, Suohui Call, Mindy Yuan, Yong Yasunaga, Mayu Kao, Winston W-Y Liu, Chia-Yang |
| Description | Author Affiliation: Zhang Y ( Edith 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.); Yeh LK ( Department 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.); Zhang S ( Edith 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.); Call M ( Edith J. Crawley Vision Research Center, Department of Ophthalmology, University of Cincinnati School of Medicine, Cincinnati, OH 45267, USA.); Yuan Y ( Edith J. Crawley Vision Research Center, Department of Ophthalmology, University of Cincinnati School of Medicine, Cincinnati, OH 45267, USA.); Yasunaga M ( Health Research Institute, National Institute of Advanced Industrial Science and Technology, Takamatsu 761-0395, Japan.); Kao WW ( Edith J. Crawley Vision Research Center, Department of Ophthalmology, University of Cincinnati School of Medicine, Cincinnati, OH 45267, USA.); Liu CY ( Edith 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.) |
| 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/ß-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 ß-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 ß-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 ß-catenin binds to and suppresses Bmp4 promoter activity. These data support the concept that cross-talk between the Wnt/ß-catenin/Bmp4 axis (in the stromal mesenchyme) and Bmp4/p63 signaling (in the epithelium) plays a pivotal role in epithelial stratification during corneal morphogenesis. |
| File Format | HTM / HTML |
| ISSN | 09501991 |
| e-ISSN | 14779129 |
| Journal | Development |
| Issue Number | 19 |
| Volume Number | 142 |
| Language | English |
| Publisher | The Company of Biologists |
| Publisher Date | 2015-10-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Discipline Developmental Discipline Biology Bone Morphogenetic Protein 4 Antagonists & Inhibitors Epithelium, Corneal Embryology Gene Expression Regulation, Developmental Physiology Morphogenesis Wnt Signaling Pathway Beta Catenin Metabolism Animals Blotting, Western Administration & Dosage Chromatin Immunoprecipitation Doxycycline Fluorescence Galactosides Histological Techniques Immunohistochemistry Indoles Low Density Lipoprotein Receptor-related Protein-5 Deficiency Low Density Lipoprotein Receptor-related Protein-6 Luciferases Mice Mice, Knockout Microscopy, Electron, Transmission Phosphoproteins Real-time Polymerase Chain Reaction Trans-activators Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Developmental Biology Molecular Biology |
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