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

Area of Science:

• Developmental biology
• Toxicology
• Molecular signaling

Background:

• 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a known teratogen linked to cleft palate.
• The precise cellular and molecular mechanisms underlying TCDD-induced cleft palate remain largely unknown.
• Wnt signaling pathways are crucial for organ development and have been implicated in TCDD's effects.

Purpose of the Study:

• To investigate the role of Wnt signaling in TCDD-induced cleft palate.
• To elucidate the cellular and molecular mechanisms by which TCDD alters palatal development.

Main Methods:

• Administration of TCDD to mice during the critical period of palate development.
• Assessment of palatal shelf cell proliferation and elevation.
• Analysis of Wnt5a and lymphoid enhancing-binding factor 1 (LEF1) activity in the developing palate.

Main Results:

• TCDD exposure impaired palatal shelf cell proliferation along the anteroposterior axis.
• TCDD administration delayed palatal shelf elevation in a significant proportion of mice.
• The activity of Wnt5a and LEF1 was significantly inhibited by TCDD in the developing palate.

Conclusions:

• Downregulation of Wnt5a and LEF1 is associated with TCDD-induced cleft palate.
• Delayed palatal shelf elevation is identified as a critical mechanism contributing to TCDD's teratogenicity.
• These findings provide insights into the molecular pathways affected by TCDD during palate development.