Deciphering TGF-ß3 function in medial edge epithelium specification and fusion during mouse secondary palate development.

BACKGROUND: Transforming growth factor-ß3 (TGF-ß3) plays a central role in mediating secondary palate fusion along the facial midline. However, the mechanisms by which TGF-ß3 functions during secondary palate fusion are still poorly understood. RESULTS: We found that mouse cytokeratin 6α and 17 mRNAs were expressed exclusively in the palate medial edge epithelium on embryonic day 14.5, and this expression was completely abolished in Tgf-ß3 mutant embryos. In contrast, we found that Jagged2 was initially expressed throughout the palate epithelium, but was specifically down-regulated in the medial edge epithelium during palatal fusion. Jagged2 down-regulation was regulated by TGF-ß3, since Jagged2 was persistently expressed in palatal medial edge epithelium in Tgf-ß3 null mutant embryos. Moreover, addition of DAPT, a specific inhibitor of Notch signaling, partially rescued the fusion defects in Tgf-ß3 null mutant palatal shelves. CONCLUSIONS: Based on these results, together with the previous study indicating that the loss of Jagged2 function promotes embryonic oral epithelial fusion, we concluded that TGF-ß3 mediates palate fusion in part by down-regulating Jagged2 expression in palatal medial edge epithelium. In addition, cytokeratin 6α and 17 are two TGF-ß3 downstream target genes in palate medial edge epithelium differentiation.