2,3,7,8-Tetrachlorodibenzo-p-dioxin Delays Palatal Shelf Elevation and Suppresses Wnt5a and Lymphoid Enhancing-Binding Factor 1 Signaling in Developing Palate

Abstract

2,3,7,8-Tetrachlorodibenzo-p-dioxin contributes to cleft palate, but the cellular and molecular mechanisms responsible for the deleterious effect on the developing palate are unclear. Because Wnt signaling is associated with 2,3,7,8-tetrachlorodibenzo-p-dioxin in organ development, we wondered whether the malformation of the palate also results from altered Wnt signaling. The 2,3,7,8-tetrachlorodibenzo-p-dioxin administration affected cell proliferation of the anteroposterior axis of the palatal shelf and delayed shelf elevation in mice. The activity of Wnt5a and lymphoid enhancing-binding factor 1 was inhibited by 2,3,7,8-tetrachlorodibenzo-p-dioxin in the developing palate. Downregulated Wnt5a and lymphoid enhancing-binding factor 1 are associated with 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced cleft palate. Moreover, delayed shelf elevation by 2,3,7,8-tetrachlorodibenzo-p-dioxin is the crucial mechanism contributing to the high incidence of cleft palate. Our findings may help in elucidating the mechanisms of 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced cleft palate.