AUTHOR=Yu Wenli , Zhang Yanping , Ruest L. Bruno , Svoboda Kathy K.

TITLE=Analysis of Snail1 function and regulation by Twist1 in palatal fusion

JOURNAL=Frontiers in Physiology

VOLUME=4

YEAR=2013

URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2013.00012

DOI=10.3389/fphys.2013.00012

ISSN=1664-042X

ABSTRACT=<p>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 <italic>Snail1</italic> gene in palatal shelves. Palatal explants treated with Snail1 siRNA did not degrade the MES and <italic>E-cadherin</italic> was not repressed leading to failure of palatal fusion. Transforming growth factor beta 3 (Tgfβ3) regulated <italic>Snail1</italic> mRNA, as <italic>Snail1</italic> expression decreased in response to <italic>Tgf</italic>β<italic>3</italic> neutralizing antibody and a PI-3 kinase (<italic>PI3K</italic>) inhibitor. Twist1, in collaboration with E2A factors, regulated the expression of <italic>Snail1</italic>. Twist1/E47 dimers bond to the <italic>Snail1</italic> promoter to activate expression. Without E47, Twist1 repressed <italic>Snail1</italic> expression. These results support the hypothesis that Tgfβ3 may signal through Twist1 and then Snail1 to downregulate <italic>E-cadherin</italic> expression during palatal fusion.</p>