Animals possess the ability to repair or regenerate certain damaged tissues. For instance, the outermost cells of the mammalian cornea are exposed to harmful conditions such as desiccation and abrasion, and these epithelial cells are continuously replaced over a matter of days. These differentiated cells are derived from a resident population of basal epithelial stem cells. Studies indicate that amphibians, including the frog Xenopus, also possess cornea stem cells. Remarkably, species of this particular frog exhibit the ability to regenerate missing lenses. These lenses are derived from the cornea, and historically this process has been described as one involving transdifferentiation of cornea epithelial cells. In fact, data from our lab suggests that these lenses are not derived from the differentiated epithelial cells, but rather from the basal cornea epithelial stem cells and/or their transient amplifying progeny. Using transgenic approaches, we have been characterizing the lineage of these cells. We are also examining components of the cornea epithelial stem cell niche, which appear to be required for the maintenance of these stem cells, as well as successful lens regeneration.
The main goal of our research is to understand the molecular and cellular events that regulate the biology of cornea stem cells, and their potential to generate additional cell fates, such as lens cells.
In earlier studies we prepared a subtracted cDNA library enriched for genes expressed during cornea-lens regeneration in Xenopus. Significantly, many of these genes are also expressed during embryonic lens formation. Efforts continue to understand the role of these genes. These studies will elucidate the relationship between embryonic lens fromation and lens regeneration.
Experiments indicate that diffusible signals are transmitted from retinal tissue that trigger the cornea epithelium to form a new lens. Our lab is also examining the role of specific cell signaling pathways in controlling this process, including FGF, retinoic acid, TGF-beta and Wnt signaling, which are also known to play key roles in eye/lens development and differentiation.
An understanding of the factors that allow some animals to repair and regenerate complete organs, such as the cornea and lens, will lead to the development of novel therapeutic approaches to treat disease and injury in humans.