Abstract
Palatal fusion is a tightly controlled process which comprises multiple cellular events, including cell movement and differentiation. Midline epithelial seam (MES) degradation is essential to palatal fusion. In this study, we analyzed the function of Snail1 during the degradation of the MES. We also analyzed the mechanism regulating the expression of the Snail1 gene in palatal shelves. Palatal explants treated with Snail1 siRNA did not degrade the MES and E-cadherin was not repressed leading to failure of palatal fusion. Transforming growth factor beta 3 (Tgfβ3) regulated Snail1 mRNA, as Snail1 expression decreased in response to Tgfβ3 neutralizing antibody and a PI-3 kinase (PI3K) inhibitor. Twist1, in collaboration with E2A factors, regulated the expression of Snail1. Twist1/E47 dimers bond to the Snail1 promoter to activate expression. Without E47, Twist1 repressed Snail1 expression. These results support the hypothesis that Tgfβ3 may signal through Twist1 and then Snail1 to downregulate E-cadherin expression during palatal fusion.
Highlights
Secondary palatal fusion is a tightly controlled process that has been described in many reviews and research papers (Ferguson, 1988; Jugessur and Murray, 2005; Gritli-Linde, 2007; Nawshad, 2008; Yu et al, 2009)
In control palates and scrambled siRNA groups the palate completely fused without evidence of midline epithelial seam (MES) E-cadherin expressing epithelial cells in the mesenchyme (Figure 1B)
In palatal shelves treated with 100 nM Snail1 siRNA, the epithelial seam broke down and degraded but triangular clusters of E-cadherinpositive epithelial cells were found primarily on the nasal side (Figure 1B, arrow)
Summary
Secondary palatal fusion is a tightly controlled process that has been described in many reviews and research papers (Ferguson, 1988; Jugessur and Murray, 2005; Gritli-Linde, 2007; Nawshad, 2008; Yu et al, 2009). The two palatal shelves initiate as outgrowth from the inner wall of the maxillary prominences as early as embryonic day (E) 12 in mice. They first grow lateral to the tongue and later become reoriented rostral to the tongue. At E14, the shelves contact and adhere at the midline, where the epithelium covering the tip of the palatal shelves forms a seam termed the midline epithelial seam (MES). The seam breaks down to achieve mesenchymal confluence. The mechanisms for this midline MES degradation are not clear and great interest has been raised on this developmental event since failure of this process results in cleft palate
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