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Updated: Aug 14, 2026
Prediction and Validation of Gene Regulatory Elements Activated During Retinoic Acid Induced Embryonic Stem Cell Differentiation
Published on: June 21, 2016
Retinoic acid down-regulates Tbx1 expression in vivo and in vitro
Catherine Roberts1, Sarah M Ivins, Chela T James
1Molecular Medicine Unit, Institute of Child Health, London WC1N 1EH, United Kingdom. c.roberts@ich.ucl.ac.uk
Abstract:
Both Tbx1 and retinoic acid (RA) are key players in embryonic pharyngeal development; loss of Tbx1 produces DiGeorge syndrome-like phenotypes in mouse models as does disruption of retinoic acid homeostasis. We have demonstrated that perturbation of retinoic acid levels in the avian embryo produces altered Tbx1 expression. In vitamin A-deficient quails, which lack endogenous retinoic acid, Tbx1 expression patterns were disrupted early in development and expression was subsequently lost in all tissues. "Gain-of-function" experiments where RA-soaked beads were grafted into the pharyngeal region produced localized down-regulation of Tbx1 expression. In these embryos, analysis of Shh and Foxa2, upstream control factors for Tbx1, suggested that the effect of RA was independent of this regulatory pathway. Real-time polymerase chain reaction analysis of retinoic acid-treated P19 cells showed a dose-dependent repression of Tbx1 by retinoic acid. Repression of Tbx1 transcript levels was first evident after 8-12 hr in culture in the presence of retinoic acid, and to achieve the highest levels of repression, de novo protein synthesis was required.
Insights
Retinoic acid (RA) impacts embryonic development by altering Tbx1 expression. This study shows RA represses Tbx1, independent of Shh and Foxa2, requiring new protein synthesis for full effect.
Area of Science:
- Developmental Biology
- Molecular Biology
Background:
- Tbx1 and retinoic acid (RA) are crucial for embryonic pharyngeal development.
- Tbx1 loss causes DiGeorge syndrome-like phenotypes; RA disruption also impacts development.
Purpose of the Study:
- To investigate the regulatory relationship between retinoic acid and Tbx1 expression during avian embryonic development.
- To determine if RA affects Tbx1 expression independently of known upstream factors like Shh and Foxa2.
Main Methods:
- Vitamin A-deficient quail embryos were used to study the effects of endogenous RA absence.
- RA-soaked beads were grafted into avian embryos to observe localized RA effects.
- Real-time PCR analyzed Tbx1 expression in RA-treated P19 cells.
Main Results:
- Vitamin A deficiency led to disrupted and eventual loss of Tbx1 expression in quail embryos.
- Localized RA application caused down-regulation of Tbx1 expression.
- RA repressed Tbx1 expression in P19 cells in a dose-dependent manner, requiring de novo protein synthesis.
Conclusions:
- Retinoic acid negatively regulates Tbx1 expression during pharyngeal development.
- RA's effect on Tbx1 is independent of the Shh and Foxa2 regulatory pathway.
- De novo protein synthesis is necessary for RA-mediated repression of Tbx1.
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