Hes1 Regulates Corneal Development and the Function of Corneal Epithelial Stem/Progenitor Cells

• Published in: Stem cells (Dayton, Ohio) Vol. 26; no. 5; pp. 1265 - 1274
• Main Authors: Nakamura, Takahiro, Ohtsuka, Toshiyuki, Sekiyama, Eiichi, Cooper, Leanne J., Kokubu, Hiroshi, Fullwood, Nigel J., Barrandon, Yann, Kageyama, Ryoichiro, Kinoshita, Shigeru
• Format: Journal Article
• Language: English
• Published: Bristol John Wiley & Sons, Ltd 01.05.2008
• Subjects: Animals; Basic Helix-Loop-Helix Transcription Factors - genetics; Basic Helix-Loop-Helix Transcription Factors - metabolism; Cell Culture Techniques; Cell Differentiation; Cell Proliferation; Cornea; Cornea - embryology; Cornea - pathology; Development; Epithelium, Corneal - cytology; Epithelium, Corneal - metabolism; Gene Expression Regulation, Developmental; Hes; Homeodomain Proteins - genetics; Homeodomain Proteins - metabolism; Mice; Mice, Knockout; Morphogenesis; Notch; Phenotype; Stem cell; Stem Cells - cytology; Stem Cells - metabolism; Time Factors; Transcription Factor HES-1; Wound Healing
• ISSN: 1066-5099; 1549-4918
• DOI: 10.1634/stemcells.2007-1067

Hes1, a major target gene in Notch signaling, regulates the fate and differentiation of various cell types in many developmental systems. To gain a novel insight into the role of Hes1 in corneal tissue, we performed gain‐of‐function and loss‐of‐function studies. We show that corneal development was severely disturbed in Hes1‐null mice. Hes1‐null corneas manifested abnormal junctional specialization, cell differentiation, and less cell proliferation ability. Worthy of note, Hes1 is expressed mainly in the corneal epithelial stem/progenitor cells and is not detected in the differentiated corneal epithelial cells. Expression of Hes1 is closely linked with corneal epithelial stem/progenitor cell proliferation activity in vivo. Moreover, forced Hes1 expression inhibits the differentiation of corneal epithelial stem/progenitor cells and maintains these cells' undifferentiated state. Our data provide the first evidence that Hes1 regulates corneal development and the homeostatic function of corneal epithelial stem/progenitor cells. Disclosure of potential conflicts of interest is found at the end of this article.