Abstract
Presentation Description :
The dynamics of epithelial stem cells (SC) and their progeny that contribute to the formation and maintenance of the cornea are poorly understood. This talk will focus on the use of K14CreERT2-Confetti mice, sophisticated microscopy platforms and image analysis tools, and computational modelling, to generated fate maps of these cells during steady-state and after epithelial debridement wounds. We show that keratin-14 (K14+) progenitor cells are defined and widely distributed across the embryonic (E16.5) murine cornea, after which they undergo cycles of proliferation and dispersal prior to eyelid opening. K14+ clonal patches disappear from the post-natal central cornea and are replaced by limbal-derived K14+ clonal streaks which maintain this tissue throughout life. Upon wounding, clones evolve from the limbus and move at an accelerate rate (~40-fold) to cover the defect. This heightened cell movement, concomitant with increased BrdU-positive cells in the periphery and elevated clonal expansion, resonates with the occurrence of symmetric division and the concept of Neutral Drift. These results not only provide vital clues about the biology of the cornea and its SC during embryogenesis and aging, but also the foundations of a model that can be used to interrogate perturbations of the cornea after wounding, infection and transplantation.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.