The vertebrate corneal epithelium: From early specification to constant renewal

Abstract

BACKGROUND:The cornea is an ectodermal/neural crest derivative formed through a cascade of molecular mechanisms to give rise to the specific optical features necessary for its refractory function. Moreover, during cornea formation and maturation, epithelial stem cells are sequestered to ensure a constant source for renewal in the adult. RESULTS: Recent progress in the molecular and stem cell biology of corneal morphogenesis and renewal shows that it can serves as a paradigm for epithelial /mesenchymal organ biology. This review will synthesize historical knowledge together with recent data to present a consistent overview of cornea specification, formation, maturation, and maintenance. CONCLUSIONS: This should be of interest not only to developmental biologists but also ophthalmologists, as several human vision problems are known to be rooted in defects in corneal development.

KLF4 Plays an Essential Role in Corneal Epithelial Homeostasis by Promoting Epithelial Cell Fate and Suppressing Epithelial–Mesenchymal Transition

“…19 EMT is involved in the formation of myofibroblasts that promote fibrotic lesions with excessive accumulation of fibrogenic extracellular matrix, tissue contraction, and impaired functions. 77–79 Previous studies on CE EMT have focused on its involvement in pathogenesis of pterygium 12 and OSSN.…”

Foxc1 and Foxc2 in the Neural Crest Are Required for Ocular Anterior Segment Development

“…1,2 The corneal epithelium initially consists of just one to two cell layers but proliferates and differentiates after birth into stratified squamous epithelium, which is composed of six to eight cell layers. In adult mice, the corneal epithelium is maintained by slow-dividing basal cells, which replace the superficial epithelial cells and are themselves replenished by stem cells in the corneal/limbal epithelium 3,4 (see below). Importantly, the development, maturation, and maintenance of the ocular surface are dependent on interactions between the mesenchyme and epithelium that are mediated by signaling mechanisms such as the canonical Wnt pathway.…”

Corneal Development

“…It is increasingly becoming clear that the developmental processes that lead to the formation of the cornea are under elaborate control of multiple families of signaling molecules that are associated with ocular development. The roles of morphogens (retinoic acid), signaling molecules (TGFβ, Wnt, and Fgf ), and transcription factors (Pax6, Pitx2, and Fox genes) during corneal development and the human defects associated with their mutations have been reviewed in detail, 19,25,[103][104][105][106][107][108] therefore not included in this review. The current challenge is to understand the mechanisms of how these genes interact at the periocular neural crest cell level to direct their differentiation into corneal endothelium or keratocytes.…”

“…The corneal epithelium is specified by E5, given that it does not lose Pax6 expression when challenged by mesenchyme from the dorsal dermis. 2,25 By E6, the epithelium is three-layers thick and it increases to 4-5 cell layers at E19. 26 The corneal epithelium begins to express the keratin pair (K3/K12) at about E14, 27 and it is fully developed and consists of 6-8 stratified cell layers at the time of hatching (Fig.…”