Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 102, Issue 27, Pages 9523-9528Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0503437102
Keywords
limbus; stem cell
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Funding
- Telethon [GAT0201] Funding Source: Medline
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The p63 gene generates transactivating and N-terminally truncated transcripts (Delta Np63) initiated by different promoters. Alternative splicing gives rise to three different C termini, designated alpha, beta, and gamma. In the ocular epithelium, the corneal stem cells, which are segregated in the basal layer of the limbus, contain the a isoform but not beta or gamma. Holoclones derived from the limbus are rich in a, meroclones contain little, and paraclones contain none. In normal resting corneal epithelium, p63 of all isoforms is absent. Upon corneal wounding, cells originating from the limbus and containing a migrate progressively through the epithelium of the peripheral and central cornea. in the absence of an attached limbus, no a isoform appears in the corneal epithelium. When migrating cells containing the a isoform appear in the wounded corneal epithelium, they are confined to the basal layer, but the suprabasal cells, not only of the cornea but of the limbus as well, contain mRNA encoding beta and gamma. These data support the concept that the a isoform of p63 is necessary for the maintenance of the proliferative potential of limbal stem cells and their ability to migrate over the cornea. The beta and gamma isoforms, being suprabasal and virtually absent from the resting limbus, are not stem cell markers but are likely to play a role in epithelial differentiation specifically during the process of corneal regeneration.
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