Search

The dynamics of epithelial stem cells (SCs) that contribute to the formation and maintenance of the cornea are poorly understood. Here, we used K14CreER T2 -Confetti (Confetti) mice, sophisticated imaging, and computational modeling to trace the origins and fate of these cells during embryogenesis and adult life. We show that keratin-14 (K14 + )-expressing progenitors are defined and widely distributed across the E16.5 cornea, after which they undergo cycles of proliferation and dispersal prior to eyelid opening. K14 + clonal patches disappear from the central cornea and are replaced by limbal-derived K14 + streaks, a finding that aligned with bromodeoxyuridine label-retaining studies. We also elucidated the mechanism by which SC clones are lost during life and propose this is due to population asymmetry and neutral drift. Finally, we established that the occurrence of an equatorial migratory mid-line is a consequence of apoptosis in a narrow nasal-temporal region, the site where eyelids meet during blinking., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Maintaining the structure of the cornea is essential for high-quality vision. In adult mammals, corneal epithelial cells emanate from stem cells in the limbus, driven by an unknown mechanism towards the centre of the cornea as cohesive clonal groups. Here we use complementary mathematical and biological models to show that corneal epithelial cells can self-organize into a cohesive, centripetal growth pattern in the absence of external physiological cues. Three conditions are required: a circumferential location of stem cells, a limited number of cell divisions and mobility in response to population pressure. We have used these complementary models to provide explanations for the increased rate of centripetal migration caused by wounding and the potential for stem cell leakage to account for stable transplants derived from central corneal tissue, despite the predominantly limbal location of stem cells.