Positive influence of AP-2alpha transcription factor on cadherin gene expression and differentiation of the ocular surface.
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.
West-Mays
Judith A
JA
Department of Pathology and Molecular Medicine, McMaster University, Health Sciences Center, Hamilton, ON, Canada. westmayj@mcmaster.ca
Sivak
Jeremy M
JM
Papagiotas
Steve S
SS
Kim
Jennifer
J
Nottoli
Timothy
T
Williams
Trevor
T
Fini
M Elizabeth
ME
D000818:Animals; D015820:Cadherins / Q000235:genetics*; D002448:Cell Adhesion; D002454:Cell Differentiation; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000502:physiology*; D005123:Eye / Q000166:cytology / Q000196:embryology; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D051379:Mice; D009799:Ocular Physiological Phenomena; D012333:RNA, Messenger / Q000235:genetics; D011817:Rabbits; D050656:Transcription Factor AP-2; D014157:Transcription Factors / Q000235:genetics* / Q000502:physiology*; D014162:Transfection
D015820:Cadherins; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; C493668:Tfap2a protein, mouse; C493669:Tfap2b protein, mouse; D050656:Transcription Factor AP-2; D014157:Transcription Factors