Ap-2 and ocular epithelial morphogenesis

Purpose. Accumulating evidence from our laboratory suggests that AP-2 transcription factor plays an important role in the maintenance and repair of the corneal epithelium. In the current study we further pursue the function of AP-2 proteins in ocular epithelial regeneration and embryogenesis. Methods. AP-2 protein was immunolocalized to the developing ocular epithelium in mouse. A detailed morphological examination of the ocular defects of AP-2 knockout mice was made using routine histological techniques. In cell culture, we over-expressed wild-type AP-2 in the rabbit corneal epithelial cell line SIRC. Results. Immunolocalization analysis revealed that AP-2 is expressed early during murine embryogenesis (E 9.5) in the thickened lens placode. During later stages (E12), AP-2 expression is restricted to the lens epithelium and the overlying surface ectoderm, destined to become the corneal epithelium. Expression is not evident in the elongating primary lens fibers. AP-2 is also expressed in the migrating neural crest cells which form the corneal stroma. Immunolocalization to additional embryonic stages and to the healing corneal epithelium in the adult further demonstrate that AP-2 is temporally and spatially expressed during ocular epithelial morphogenesis. Homozygous AP-2 null mice exhibit either retardation of lens formation or replacement of developing lens with abnormally migrating neural crest cells. SIRC cells stably transformed with wild-type AP-2 express significant amounts of AP-2 mRNA, protein, and show increased DNA binding activity for an AP-2 specific oligonucleotide. These clones also exhibit a drastically altered phenotype and decreased cell adhesion. Conclusions. Together, these findings demonstrate that AP-2 is an essential factor for ocular epithelial development, the function of which may be to regulate cell adhesion.