Corneal epithelial cell fate is maintained during repair by Notch1 signaling via the regulation of vitamin A metabolism
Details
Serval ID
serval:BIB_BB45AEF027F4
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Corneal epithelial cell fate is maintained during repair by Notch1 signaling via the regulation of vitamin A metabolism
Journal
Developmental Cell
ISSN
1534-5807 (Print)
Publication state
Published
Issued date
08/2007
Volume
13
Number
2
Pages
242-53
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Aug
Research Support, Non-U.S. Gov't --- Old month value: Aug
Abstract
Integrity and preservation of a transparent cornea are essential for good vision. The corneal epithelium is stratified and nonkeratinized and is maintained and repaired by corneal stem cells. Here we demonstrate that Notch1 signaling is essential for cell fate maintenance of corneal epithelium during repair. Inducible ablation of Notch1 in the cornea combined with mechanical wounding show that Notch1-deficient corneal progenitor cells differentiate into a hyperplastic, keratinized, skin-like epithelium. This cell fate switch leads to corneal blindness and involves cell nonautonomous processes, characterized by secretion of fibroblast growth factor-2 (FGF-2) through Notch1(-/-) epithelium followed by vascularization and remodeling of the underlying stroma. Vitamin A deficiency is known to induce a similar corneal defect in humans (severe xerophthalmia). Accordingly, we found that Notch1 signaling is linked to vitamin A metabolism by regulating the expression of cellular retinol binding protein 1 (CRBP1), required to generate a pool of intracellular retinol.
Keywords
Animals
Cell Differentiation
*Cell Lineage
Cell Movement
Corneal Stroma/pathology
Epidermis/cytology
Epithelium, Corneal/*cytology/pathology
Keratins/metabolism
Meibomian Glands/abnormalities
Mice
Models, Biological
Receptor, Notch1/deficiency/*metabolism
Retinol-Binding Proteins/metabolism
*Signal Transduction
Stem Cells/cytology
Vitamin A/*metabolism
*Wound Healing
Pubmed
Web of science
Open Access
Yes
Create date
28/01/2008 11:39
Last modification date
20/08/2019 15:29