title: The "replacement hypothesis":  corneal stem cell origin epithelia are replaced by limbal stem cell origin epithelia in mouse cornea during maturation.
abstract: OBJECTIVE
  Previous studies have shown that the stem cells of corneal epithelia are located at the limbal basal layer. Limbal stem cells are believed to be the source of corneal epithelial cell proliferation and differentiation. This study tested the replacement hypothesis, which suggests that corneal stem cell origin epithelia may be replaced by limbal stem cell origin epithelia after 2 weeks of age in mice.
  
  
  METHODS
  The cytokeratin 12 expression pattern in the cornea was examined using K12 IRES-Cre and Cre reporter mice.
  
  
  RESULTS
  Before 2 weeks of age, K12 expression in corneal epithelia showed a mosaic pattern. After 2 weeks of age, centripetal K12 IRES-Cre expression gradually elongated from the limbal area. Around 12 weeks of age, the mosaic expression pattern disappeared from the center of the cornea. Temporal and spatial observations of K12 IRES-Cre expression patterns suggested that the mosaic pattern cells proliferated and amassed at the same position from day 15.5 of the embryonic stage at the latest.
  
  
  CONCLUSIONS
  Therefore, these cells were considered corneal stem cell origin epithelia. In contrast, centripetal pattern cell populations were considered limbal stem cell origin epithelia because they originated from the limbal area and moved to the center of the cornea. These observations suggest that corneal stem cell origin epithelia are replaced by limbal stem cell origin epithelia after 2 weeks of age in mice.
authors.affiliation: Department of Ophthalmology, Ehime University School of Medicine, Ehime, Japan. yhayashi@m.ehime-u.ac.jp
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Hayashi
authors.forename: Narumi
authors.initials: N
authors.lastname: Watanabe
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Ohashi
mesh_terms: D000818:Animals; D019070:Cell Lineage; D002465:Cell Movement; D019573:Epithelium, Corneal / Q000166:cytology* / Q000378:metabolism; D005260:Female; D049452:Green Fluorescent Proteins / Q000378:metabolism; D053551:Keratin-12 / Q000378:metabolism; D016850:Limbus Corneae / Q000166:cytology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism
chemical_list: D053551:Keratin-12; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins