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

Stem Cells. 2008 May;26(5):1265-74. doi: 10.1634/stemcells.2007-1067. Epub 2008 Feb 21.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism*
  • Cell Culture Techniques
  • Cell Differentiation
  • Cell Proliferation
  • Cornea / embryology*
  • Cornea / pathology
  • Epithelium, Corneal / cytology*
  • Epithelium, Corneal / metabolism*
  • Gene Expression Regulation, Developmental
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism*
  • Mice
  • Mice, Knockout
  • Morphogenesis
  • Phenotype
  • Stem Cells / cytology
  • Stem Cells / metabolism*
  • Time Factors
  • Transcription Factor HES-1
  • Wound Healing


  • Basic Helix-Loop-Helix Transcription Factors
  • Hes1 protein, mouse
  • Homeodomain Proteins
  • Transcription Factor HES-1