Hes1 regulates corneal development and the function of corneal epithelial stem/progenitor cells

T Nakamura, T Ohtsuka, E Sekiyama, LJ Cooper… - Stem …, 2008 - academic.oup.com
T Nakamura, T Ohtsuka, E Sekiyama, LJ Cooper, H Kokubu, NJ Fullwood, Y Barrandon
Stem cells, 2008academic.oup.com
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 …
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 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.
Oxford University Press