| Autor: |
Walker H; Health Sciences Centre, McMaster University, 1280 Main St. W, Hamilton, ON L8S 4L8, Canada., Taiyab A; Health Sciences Centre, McMaster University, 1280 Main St. W, Hamilton, ON L8S 4L8, Canada., Deschamps P; Health Sciences Centre, McMaster University, 1280 Main St. W, Hamilton, ON L8S 4L8, Canada., Williams T; Department of Craniofacial Biology, University of Colorado, Mail Stop 8120, RC1-S, Rm L18 11111, 12801 E. 17th Ave, Aurora, CO 80045, USA., West-Mays JA; Health Sciences Centre, McMaster University, 1280 Main St. W, Hamilton, ON L8S 4L8, Canada. |
| Abstrakt: |
The cornea is an anterior eye structure specialized for vision. The corneal endothelium and stroma are derived from the periocular mesenchyme (POM), which originates from neural crest cells (NCCs), while the stratified corneal epithelium develops from the surface ectoderm. Activating protein-2β (AP-2β) is highly expressed in the POM and important for anterior segment development. Using a mouse model in which AP-2β is conditionally deleted in the NCCs (AP-2β NCC KO), we investigated resulting corneal epithelial abnormalities. Through PAS and IHC staining, we observed structural and phenotypic changes to the epithelium associated with AP-2β deletion. In addition to failure of the mutant epithelium to stratify, we also observed that Keratin-12, a marker of the differentiated epithelium, was absent, and Keratin-15, a limbal and conjunctival marker, was expanded across the central epithelium. Transcription factors PAX6 and P63 were not observed to be differentially expressed between WT and mutant. However, growth factor BMP4 was suppressed in the mutant epithelium. Given the non-NCC origin of the epithelium, we hypothesize that the abnormalities in the AP-2β NCC KO mouse result from changes to regulatory signaling from the POM-derived stroma. Our findings suggest that stromal pathways such as Wnt/β-Catenin signaling may regulate BMP4 expression, which influences cell fate and stratification. |
