Editors' ChoiceCELL FATE

Notch Sees Clearly

Science's STKE  21 Aug 2007:
Vol. 2007, Issue 400, pp. tw299
DOI: 10.1126/stke.4002007tw299

To maintain the clarity required for light to reach the retina, the upper epidermal cells of the cornea are not keratinized and the lower stroma has no vasculature. Aberrant development of an opaque cornea after injury or disease is one of the leading causes of blindness. Vauclair et al. showed that mice with a skin-specific deficiency in Notch1, a receptor important for embryonic and postnatal development, developed corneal hyperplasia. Histopathological analysis showed that the corneal epithelia of Notch1-deficient mice became keratinized and thickened in comparison with those of wild-type mice. Corneal epithelial cells of Notch1-deficient mice were hyperproliferative as assessed by immunohistochemical detection of Ki67 (an antigen associated with actively growing cells), and the stroma of Notch1-deficient mice became vascularized. Notch1 deficiency also resulted in a loss of functional meibomian glands, which secrete a lipid layer that protects the eye from irritants. This led the authors to examine the role of wounding in initiating keratinization of the corneal epithelium. Whereas wounding of wild-type animals resulted in recovery of the epithelium, wounding of Notch1-deficient animals resulted in occlusion of the cornea and the expression of skin-specific keratins. DNA microarray analysis identified cellular retinol-binding protein (CRBP1), a protein important in the metabolism of vitamin A, as a downstream target of Notch1. Wounding of the corneal epithelium of CRBP1-deficient mice resulted in a phenotype similar to that observed in Notch1-deficient animals. These data show the importance of Notch1 in cell fate determination during wound repair and link Notch1 with vitamin A metabolism, which is important for maintaining a healthy cornea.

S. Vauclair, F. Majo, A.-D. Durham, N. B. Ghyselinck, Y. Barrandon, F. Radtke, Corneal epithelial cell fate is maintained during repair by Notch1 signaling via the regulation of vitamin A metabolism. Dev. Cell 13, 242-253 (2007). [PubMed]