Hes1 regulates corneal development and the function of corneal epithelial stem/progenitor cells.
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.
Nakamura
Takahiro
T
Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kawaramachi Hirokoji, Kamigyo-ku, Kyoto 602-0841 Japan. tnakamur@ophth.kpu-m.ac.jp
Ohtsuka
Toshiyuki
T
Sekiyama
Eiichi
E
Cooper
Leanne J
LJ
Kokubu
Hiroshi
H
Fullwood
Nigel J
NJ
Barrandon
Yann
Y
Kageyama
Ryoichiro
R
Kinoshita
Shigeru
S
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D049109:Cell Proliferation; D003315:Cornea / Q000196:embryology* / Q000473:pathology; D019573:Epithelium, Corneal / Q000166:cytology* / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009024:Morphogenesis; D010641:Phenotype; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D013997:Time Factors; D000072056:Transcription Factor HES-1; D014945:Wound Healing
D051792:Basic Helix-Loop-Helix Proteins; D018398:Homeodomain Proteins; D000072056:Transcription Factor HES-1; C489734:Hes1 protein, mouse