LAUSR

During palatogenesis, the anterior palate is covered with ortho or parakeratinized epithelium while the posterior palate is covered with non-keratinized epithelium. To elucidate the developmental mechanisms underlying these region-specific differentiation patterns of palatal epithelium along the antero-posterior axis, we employed the tissue recombination assay during in vitro organ cultivation of the developing palate at E16 for 2 days. The recombination assay results revealed that epithelial differentiation with specific localization patterns of Cytokeratin10 and Ki67 are modulated by mesenchymal tissues. Based on these results, we examined the underlying signaling regulations that modulate epithelial differentiation, using laser microdissection and genome wide screening. Our screening data suggested Meox2 (Mesenchyme homeobox 2) to be a key regulator that controls epithelial differentiation in the mesenchymal tissue. To examine the developmental function of Meox2, we employed in vitro organ cultivation along with the knockdown and overexpression of Meox2 using siRNA andMeox2 overexpression vector, respectively, at E14.5 for 2 and 4 days. After 2-day cultivation, we examined the altered expression patterns of related signaling molecules such as Shh and Bmp, using in situ hybridization and RT-qPCR. After 4-day cultivation, we examined the altered histogenesis and localization patterns of Cytokeratin10 and Ki67. Based on the restricted and specific expression of candidate mesenchymal genes and the results of the recombination assay, we conclude that posteriorly expressed Meox2 is involved in the determination of non-keratinized epithelial differentiation through complex signaling regulations in mice palatogenesis.