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

¹ Department of Ophthalmology, Kyoto Prefectural University of Medicine, Graduate School of Medicine, Kyoto 602-0841, Japan; Research Center for Regenerative Medicine, Doshisha University, Kyoto, Japan; Laboratory of Stem Cell Dynamics, Ecole Polytechnique Federale de Lausanne (EPFL) and Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland
² Institute for Virus Research, Kyoto University, Kyoto, Japan
³ Department of Ophthalmology, Kyoto Prefectural University of Medicine, Graduate School of Medicine, Kyoto 602-0841, Japan
⁴ Biomedical Sciences, Lancaster University, Lancaster, U.K.
⁵ Laboratory of Stem Cell Dynamics, Ecole Polytechnique Federale de Lausanne (EPFL) and Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland

^* To whom correspondence should be addressed. E-mail: tnakamur{at}ophth.kpu-m.ac.jp.

	Abstract

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 mainly expressed 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 provides the first evidence that Hes1 regulates corneal development and the homeostatic function of corneal epithelial stem/progenitor cells.