title: Study of corneal epithelial progenitor origin and the Yap1 requirement using keratin 12 lineage tracing transgenic mice.
abstract: Key issues in corneal epithelium biology are the mechanism for corneal epithelium stem cells to maintain the corneal epithelial homeostasis and wound healing responses, and what are the regulatory molecular pathways involved. There are apparent discrepancies about the locations of the progenitor populations responsible for corneal epithelial self-renewal. We have developed a genetic mouse model to trace the corneal epithelial progenitor lineages during adult corneal epithelial homeostasis and wound healing response. Our data revealed that the early corneal epithelial progenitor cells expressing keratin-12 originated from limbus, and gave rise to the transit amplifying cells that migrated centripetally to differentiate into corneal epithelial cells. Our results support a model that both corneal epithelial homeostasis and wound healing are mainly maintained by the activated limbal stem cells originating form limbus, but not from the corneal basal epithelial layer. In the present study, we further demonstrated the nuclear expression of transcriptional coactivator YAP1 in the limbal and corneal basal epithelial cells and its essential role for maintaining the high proliferative potential of those corneal epithelial progenitor cells in vivo.
authors.affiliation: Departments of Ophthalmology and Visual Sciences, University of Louisville School of Medicine, Louisville, KY 40202, USA.
authors.forename: Ramesh Babu
authors.initials: RB
authors.lastname: Kasetti
authors.affiliation: Departments of Ophthalmology and Visual Sciences, University of Louisville School of Medicine, Louisville, KY 40202, USA.
authors.forename: Subhash
authors.initials: S
authors.lastname: Gaddipati
authors.affiliation: Departments of Ophthalmology and Visual Sciences, University of Louisville School of Medicine, Louisville, KY 40202, USA.
authors.forename: Shifu
authors.initials: S
authors.lastname: Tian
authors.affiliation: Department of Interventional Radiology, Shanghai 10th People's Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Science and Technology, Tongji University, Shanghai 200092, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Xue
authors.affiliation: Department of Ophthalmology, University of Cincinnati, OH 45267, USA.
authors.forename: Winston W-Y
authors.initials: WW
authors.lastname: Kao
authors.affiliation: Departments of Ophthalmology and Visual Sciences, University of Louisville School of Medicine, Louisville, KY 40202, USA.|James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY 40202, USA.
authors.forename: Qingxian
authors.initials: Q
authors.lastname: Lu
authors.affiliation: Departments of Ophthalmology and Visual Sciences, University of Louisville School of Medicine, Louisville, KY 40202, USA.|James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY 40202, USA.
authors.forename: Qiutang
authors.initials: Q
authors.lastname: Li
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D018797:Cell Cycle Proteins; D019070:Cell Lineage; D019573:Epithelium, Corneal / Q000166:cytology* / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics; D053551:Keratin-12 / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D010750:Phosphoproteins / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D014945:Wound Healing; D000091102:YAP-Signaling Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; C507495:KRT12 protein, mouse; D053551:Keratin-12; D010750:Phosphoproteins; D000091102:YAP-Signaling Proteins; C486223:Yap1 protein, mouse; D049452:Green Fluorescent Proteins