Positive influence of AP-2alpha transcription factor on cadherin gene expression and differentiation of the ocular surface

Differentiation. 2003 Apr;71(3):206-16. doi: 10.1046/j.1432-0436.2003.710302.x.


The family of transcription factors Activating protein-2 (AP-2) are known to play important roles in numerous developmental events, including those associated with differentiation of stratified epithelia. However, to date, the influence of the AP-2 genes on endogenous gene expression in the stratified epithelia and how this affects differentiation has not been well defined. The following study examines the detailed expression of the AP-2alpha and AP-2beta proteins in the stratified epithelia of the ocular surface, including that in the cornea and developing eyelids. The effect of altered levels of the AP-2alpha gene on ocular surface differentiation was also examined using a corneal epithelial cell line and AP-2alpha chimeric mice. Immunolocalization studies revealed that, while AP-2beta was broadly expressed throughout all cell layers of the stratified corneal epithelium, AP-2alpha expression was confined to cell compartments more basally located. AP-2alpha was also highly expressed in the less differentiated cell layers of the eyelid epidermis. Overexpression of the AP-2alpha gene in the corneal cell line, SIRC, resulted in a dramatic change in cell phenotype including a clumping growth behavior that was distinct from the smooth monolayer of the parent cell line. Accompanying this change was an up-regulation in levels of the cell adhesion molecule, N-cadherin. Examination of the ocular surface of AP-2alpha chimeric mice, derived from a mixed population of AP-2alpha-/- and AP-2alpha+/+, revealed that a down-regulation in E-cadherin expression is correlated with location of the AP-2alpha-/- null cells. Together, these findings demonstrate that AP-2alpha participates in regulating differentiation of the ocular surface through induction in cadherin expression.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cadherins / genetics*
  • Cell Adhesion
  • Cell Differentiation
  • Cell Line
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / physiology*
  • Eye / cytology
  • Eye / embryology
  • Gene Expression Regulation, Developmental / genetics*
  • Mice
  • Ocular Physiological Phenomena*
  • RNA, Messenger / genetics
  • Rabbits
  • Transcription Factor AP-2
  • Transcription Factors / genetics*
  • Transcription Factors / physiology*
  • Transfection


  • Cadherins
  • DNA-Binding Proteins
  • RNA, Messenger
  • Tfap2a protein, mouse
  • Tfap2b protein, mouse
  • Transcription Factor AP-2
  • Transcription Factors