Retinoic acid down‐regulates <i>Tbx1</i> expression in vivo and in vitro

書誌事項

公開日
2005-02-25
権利情報
  • http://onlinelibrary.wiley.com/termsAndConditions#vor
DOI
  • 10.1002/dvdy.20268
公開者
Wiley

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説明

<jats:title>Abstract</jats:title><jats:p>Both <jats:italic>Tbx1</jats:italic> and retinoic acid (RA) are key players in embryonic pharyngeal development; loss of <jats:italic>Tbx1</jats:italic> 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 <jats:italic>Tbx1</jats:italic> expression. In vitamin A‐deficient quails, which lack endogenous retinoic acid, <jats:italic>Tbx1</jats:italic> 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 <jats:italic>Tbx1</jats:italic> expression. In these embryos, analysis of <jats:italic>Shh</jats:italic> and <jats:italic>Foxa2</jats:italic>, upstream control factors for <jats:italic>Tbx1</jats:italic>, 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 <jats:italic>Tbx1</jats:italic> by retinoic acid. Repression of <jats:italic>Tbx1</jats:italic> 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.</jats:p>

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