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Analysis of Retinoic Acid-induced Neural Differentiation of Mouse Embryonic Stem Cells in Two and Three-dimensional Embryoid Bodies
Published on: April 22, 2017
All-trans-retinoic acid alters Smads expression in embryonic neural tissue of mice
Juntao Zhang1, Rong Li, Quanren He
1Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan, Shanxi 030001, China.
Abstract:
Retinoic acid can cause malformations of the developing nervous system. Smad signaling is involved in embryonic development. The current study investigated all-trans-retinoic acid (ATRA)-induced alteration of Smad expression in the developing neural tubes of mice. Pregnant mice were treated with a single dose of 50 mg/kg ATRA by oral gavage on embryonic day E7. Western immunoblotting was used to examine Smads proteins, particularly phosphorylated (p-) Smad1, total Smad1 and Smad6 in the neural tissue of the embryos on E8-E11 following treatment. Results showed that ATRA treatment significantly increased expression of both p-Smad1 and total Smad1, while Smad6 was decreased in neural tissues of ATRA-exposed embryos in utero from E8 to E11, a critical period for neural tube formation. Data suggest that disruption of Smad signaling may be involved in ATRA-induced neural tube defects.
Insights
All-trans-retinoic acid (ATRA) exposure during embryonic development disrupts Smad signaling. This disruption in Smad proteins may contribute to the neural tube defects observed in developing embryos.
Area of Science:
- Developmental biology
- Molecular signaling
- Toxicology
Background:
- Retinoic acid is crucial for embryonic development but can cause malformations.
- Smad signaling pathways play a vital role in embryonic development.
- Neural tube defects are a significant concern in developmental toxicology.
Purpose of the Study:
- To investigate the effects of all-trans-retinoic acid (ATRA) on Smad protein expression in developing mouse neural tubes.
- To determine if Smad signaling disruption is implicated in ATRA-induced neural tube defects.
Main Methods:
- Pregnant mice were administered a single dose of ATRA (50 mg/kg) on embryonic day 7.
- Western immunoblotting was employed to analyze Smad protein levels (p-Smad1, total Smad1, Smad6) in embryonic neural tissues from E8 to E11.
- Focus on critical neural tube formation period.
Main Results:
- ATRA treatment significantly increased both phosphorylated Smad1 (p-Smad1) and total Smad1 expression.
- A significant decrease in Smad6 expression was observed in ATRA-exposed embryos.
- These alterations occurred during the critical E8-E11 period of neural tube development.
Conclusions:
- ATRA exposure alters Smad signaling pathways in the developing mouse neural tube.
- Disruption of Smad signaling is a potential mechanism underlying ATRA-induced neural tube defects.
- Further research into Smad signaling is warranted for understanding and preventing developmental neurotoxicity.

