Deciphering TGF-β3 Function in Medial Edge Epithelium Specification and Fusion During Mouse Secondary Palate Development

Background: Transforming growth factor-3 (TGF-3) plays a central role in mediating secondary palate fusion along the facial midline. However, the mechanisms by which TGF-3 functions during secondary palate fusion are still poorly understood. Results: We found that mouse cytokeratin 6 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-3 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-3, since Jagged2 was persistently expressed in palatal medial edge epithelium in Tgf-3 null mutant embryos. Moreover, addition of DAPT, a specific inhibitor of Notch signaling, partially rescued the fusion defects in Tgf-3 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-3 mediates palate fusion in part by down-regulating Jagged2 expression in palatal medial edge epithelium. In addition, cytokeratin 6 and 17 are two TGF-3 downstream target genes in palate medial edge epithelium differentiation. Developmental Dynamics 243:1536-1543, 2014. (c) 2014 Wiley Periodicals, Inc.