Retinoic acid down-regulates Tbx1 expression in vivo and in vitro
Version of Record online: 25 FEB 2005
Copyright © 2005 Wiley-Liss, Inc.
Volume 232, Issue 4, pages 928–938, April 2005
How to Cite
Roberts, C., Ivins, S. M., James, C. T. and Scambler, P. J. (2005), Retinoic acid down-regulates Tbx1 expression in vivo and in vitro. Dev. Dyn., 232: 928–938. doi: 10.1002/dvdy.20268
- Issue online: 23 MAR 2005
- Version of Record online: 25 FEB 2005
- Manuscript Accepted: 23 SEP 2004
- Manuscript Revised: 16 SEP 2004
- Manuscript Received: 16 JUN 2004
- British Heart Foundation. Grant Number: RG/2000006
- avian embryo;
- retinoic acid;
- pharyngeal development
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. Developmental Dynamics 232:928–938, 2005. © 2005 Wiley-Liss, Inc.