title: Rare corneal clones in mice suggest an age-related decrease of stem cell activity and support the limbal epithelial stem cell hypothesis.
abstract: The anterior ocular surface comprises the cornea, conjunctiva and a narrow intermediate region called the limbus. It is widely accepted that the corneal epithelium is maintained by stem cells but different hypotheses propose that the stem cells that maintain the mouse corneal epithelium during normal homeostasis are located either in the basal limbal epithelium or throughout the basal corneal epithelium. There are no specific markers to help test these alternatives and new methods are required to distinguish between them. We observed that KRT5(LacZ/-) transgenic mice produced rare β-galactosidase (β-gal)-positive radial stripes in the corneal epithelium. These stripes are likely to be clonal lineages of cells derived from stem cells, so they provide a lineage marker for actively proliferating stem cells. The distributions of the β-gal-positive radial stripes suggested they extended centripetally from the limbus, supporting the limbal epithelial stem cell (LESC) hypothesis. Stripe frequency declined between 15 and 30 weeks, which predicts a reduction in stem cell function with age. Pax6(+/-), KRT5(LacZ/-) corneas had small patches rather than stripes, which confirms that corneal maintenance is abnormal in Pax6(+/-) mice.
authors.affiliation: Division of Reproductive and Developmental Sciences, Genes and Development Group, University of Edinburgh, Edinburgh EH8 9XD, Scotland, UK.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Douvaras
authors.forename: Sheila
authors.initials: S
authors.lastname: Webb
authors.forename: Duncan A
authors.initials: DA
authors.lastname: Whitaker
authors.forename: Natalie
authors.initials: N
authors.lastname: Dorà
authors.forename: Robert E
authors.initials: RE
authors.lastname: Hill
authors.forename: Julia R
authors.initials: JR
authors.lastname: Dorin
authors.forename: John D
authors.initials: JD
authors.lastname: West
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D002999:Clone Cells; D004847:Epithelial Cells / Q000166:cytology*; D019573:Epithelium, Corneal / Q000166:cytology* / Q000378:metabolism; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism; D005838:Genotype; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D053555:Keratin-5 / Q000378:metabolism; D016850:Limbus Corneae / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D013194:Staining and Labeling; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D005136:Eye Proteins; D018398:Homeodomain Proteins; D053555:Keratin-5; D000071841:PAX6 Transcription Factor; C000605730:PAX6 protein, human; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; D012097:Repressor Proteins; D001616:beta-Galactosidase