| First Author | Chen L | Year | 2016 |
| Journal | Invest Ophthalmol Vis Sci | Volume | 57 |
| Issue | 3 | Pages | 1072-81 |
| PubMed ID | 26968737 | Mgi Jnum | J:254639 |
| Mgi Id | MGI:6112499 | Doi | 10.1167/iovs.15-18103 |
| Citation | Chen L, et al. (2016) AP-2beta Is a Downstream Effector of PITX2 Required to Specify Endothelium and Establish Angiogenic Privilege During Corneal Development. Invest Ophthalmol Vis Sci 57(3):1072-81 |
| abstractText | PURPOSE: The homeodomain transcription factor, PITX2, is at the apex of a genetic pathway required for corneal development, but the critical effector genes regulated by the PITX2 remain unknown. The purpose of this study was to discover and validate PITX2-dependent mechanisms required for specifying cell lineages and establishing angiogenic privilege within the developing cornea. METHODS: Microarrays were used to compare gene expression in corneas isolated from temporal Pitx2 knockout embryos and control littermates. Quantitative RT-PCR and immunohistochemistry was used to further validate Tfap2b expression differences in Pitx2 knockout versus control corneas. In situ hybridization and protein immunohistochemistry were used to assay eyes of a Tfap2b allelic series of embryos to identify differentiated cellular lineages in the cornea, blood vessel endothelium, or lymphatic vessel endothelium. RESULTS: We show that PITX2 is required for the expression of Tfap2b, encoding the AP-2beta transcription factor, in the neural crest during corneal development. Markers of differentiated corneal epithelium and stroma are expressed in the absence of AP-2beta. In contrast, markers of differentiated corneal endothelium are not expressed in the absence of AP-2beta. Endomucin+ blood vessels are present throughout the developing corneal stroma in the absence of AP-2beta, whereas LYVE1+ lymphatic vessels are not found. CONCLUSIONS: The AP-2beta transcription factor is an important effector of PITX2 function during corneal development, required for differentiation of corneal endothelium and establishment of angiogenic privilege. Unlike PITX2, AP-2beta is not required for the early expression of available lineage specific markers for the corneal epithelium and stroma during embryogenesis, nor establishment of lymphangiogenic privilege. Therefore, additional PITX2-dependent factors likely regulate these latter processes during embryonic development. These results extend our understanding of the genetic mechanisms regulating cornea development. |
