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TISSUE-SPECIFIC STEM CELLS

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

^aDepartment of Ophthalmology, Kyoto Prefectural University of Medicine, Graduate School of Medicine, Kyoto, Japan;
^bResearch Center for Regenerative Medicine, Doshisha University, Kyoto, Japan;
^cLaboratory of Stem Cell Dynamics, Ecole Polytechnique Federale de Lausanne and Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland;
^dInstitute for Virus Research, Kyoto University, Kyoto, Japan;
^eBiomedical Sciences, Lancaster University, Lancaster, United Kingdom

Key Words. Cornea • Development • Hes • Notch • Stem cell

Correspondence: Takahiro Nakamura M.D., Ph.D., Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kawaramachi Hirokoji, Kamigyo-ku, Kyoto 602-0841 Japan. Telephone: 81-75-251-5578; Fax: 81-75-251-5663; e-mail: tnakamur{at}ophth.kpu-m.ac.jp

Received December 14, 2007; accepted for publication February 12, 2008.
First published online in STEM CELLS EXPRESS   February 21, 2008.



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.