| During palatal fusion, the midline epithelial seam between the palatal shelves degrades to achieve mesenchymal confluence. Morphological and molecular evidence support the theory that the epithelial-mesenchymal transition (EMT) is one of the mechanisms that regulate palatal fusion. Transforming growth factor (TGF)-beta signaling plays a role in palatal EMT by regulating the expression of EMT related transcription factors, such as Snail1 and Twist1. In our experiments, we captured the palatal fusion process using live cell imaging technique. During fusion, the medial edge epithelial (MEE) cells were migrating, supporting that EMT contributed to palatal fusion. When Twist1 or Snail1 expression was suppressed, the palatal fusion was delayed. Twist1 or Snail1 expression was in response to TGFbeta3 or PI3K. Twist1 formed dimers with E2A (E12/E47) proteins in palatal tissue and bound to Snail1 promoter, suggesting Twist1 cooperated with E2A to regulate Snail1 expression. In cultured cells, evidence demonstrated that forced dimer of Twist1/E2A activated Snail1 promoter activity. |
