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Published on: November 6, 2014
[Inhibition of pSmad implicated in cleft palate induced by all-trans retinoic acid]
Xiaozhuan Liu1, Hang Zhang, Yan Xu
1Basic Medical College of Zhengzhou University, Zhengzhou 450001, China.
Objective:
To investigate the effects of excessive all-trans retinoic acid (atRA) on palatogenesis in mouse fetuses and level of Smad2 phophorylation (pSmad2).
Methods:
atRA (80 mg/kg x d) was orally given to mice on embryonic day 11 (E11). Palatal fusion was examined by Hemagglutinin Esterase (HE). The level of Smad2 phophorylation (pSmad2) in medial edge epithelial (MEE) was detected by immunohistochemistry and Western Blot, respectively.
Results:
The incidence of cleft palate (CP) was 90% of total fetus in atRA-treated group. Compared with vehicle control group, no pSmad2 was identified in MEE in atRA-treated palatal shelves, which was correlated with the persistence of the MEE and failure of palatal fusion.
Conclusion:
Inhibition of Smad phosphorylation might be involved in cleft palate induced by atRA.
Insights
Excessive all-trans retinoic acid (atRA) exposure in mice caused a 90% incidence of cleft palate. This occurred because atRA inhibited Smad2 phosphorylation, preventing palatal fusion.
Area of Science:
- Developmental biology
- Molecular biology
- Teratology
Context:
- All-trans retinoic acid (atRA) is crucial for embryonic development.
- Excessive atRA exposure is a known teratogen, leading to birth defects.
- Palatogenesis, the process of palate formation, is sensitive to retinoid signaling.
Purpose:
- To investigate the teratogenic effects of excessive all-trans retinoic acid (atRA) on mouse palatogenesis.
- To determine the impact of atRA on Smad2 phosphorylation levels in the medial edge epithelium (MEE) during palate development.
Summary:
- Mice exposed to high-dose atRA (80 mg/kg) on embryonic day 11 exhibited a 90% incidence of cleft palate.
- Immunohistochemistry and Western Blot analysis revealed a complete absence of phosphorylated Smad2 (pSmad2) in the MEE of atRA-treated fetuses.
- The lack of pSmad2 correlated with persistent MEE and failed palatal fusion, indicating a disruption in the TGF-beta/BMP signaling pathway.
Impact:
- This study suggests that the inhibition of Smad phosphorylation is a key mechanism underlying atRA-induced cleft palate.
- Findings highlight the critical role of Smad2 phosphorylation in normal palatal fusion.
- Provides insights into the molecular pathways affected by retinoid teratogenicity, relevant for understanding birth defect etiology.
