Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
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TY - JOUR
T1 - Hes1 regulates corneal development and the function of corneal epithelial stem/progenitor cells
AU - Nakamura, Takahiro
AU - Ohtsuka, Toshiyuki
AU - Sekiyama, Eiichi
AU - Cooper, Leanne J.
AU - Kokubu, Hiroshi
AU - Fullwood, Nigel J.
AU - Barrandon, Yann
AU - Kageyama, Ryoichiro
AU - Kinoshita, Shigeru
PY - 2008/5
Y1 - 2008/5
N2 - 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.
AB - 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.
KW - cornea
KW - development
KW - Hes
KW - Notch
KW - stem cell
KW - CENTRAL-NERVOUS-SYSTEM
KW - HELIX FACTOR HES-1
KW - NEURAL STEM-CELLS
KW - TRANSCRIPTION FACTOR
KW - MAMMALIAN HAIRY
KW - NOTCH
KW - DIFFERENTIATION
KW - P63
KW - EXPRESSION
KW - ENHANCER
UR - http://www.scopus.com/inward/record.url?scp=46749138776&partnerID=8YFLogxK
U2 - 10.1634/stemcells.2007-1067
DO - 10.1634/stemcells.2007-1067
M3 - Journal article
VL - 26
SP - 1265
EP - 1274
JO - Stem Cells
JF - Stem Cells
SN - 1066-5099
IS - 5
ER -