Notch1 and Corneal Cell Fate

Abstract

I very much enjoyed reading a Developmental Cell paper from Freddy Radtke's laboratory describing exciting findings regarding the requirement of Notch1 signaling for maintenance of corneal integrity during wound repair. The authors showed that Notch1 controls corneal cell fate and prevents keratinization and tissue differentiation into a skin-like epithelium, which is causal to corneal blindness. They further demonstrated that this effect is through negative control of FGF-2 and vascularization and through positive control of vitamin A metabolism. These results provided novel insights into the role of Notch1 as a master regulator of corneal cell fate to prevent skin-like epithelium formation upon injury. I consider these findings particularly interesting because Notch1 signaling in the epidermis is not only required for normal epidermal stratification, differentiation, and skin tumor suppression but is also required for the prevention of cell fate changes upon stress. This discovery serves as a basis for further investigations into the importance of Notch 1 for corneal blindness and also provides a platform to study the differential effects of Notch1 expression in other epithelial cell types and its regulation by upstream or downstream effectors. This PaperPick refers to Corneal Epithelial Cell Fate Is Maintained during Repair by Notch1 Signaling via the Regulation of Vitamin A Metabolism, by S. Vauclair, F. Majo, A.-D. Durham, N. B. Ghyselinck, Y. Barrandon, and F. Radtke, published in August 2007. Video Abstract Freddy Radtke and Craig Nowell discuss what led to the 2007 Vauclair et al. study and the implications of its findings.