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Retinoic acid down‐regulates Tbx1 expression in vivo and in vitro
Author(s) -
Roberts Catherine,
Ivins Sarah M.,
James Chela T.,
Scambler Peter J.
Publication year - 2005
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/dvdy.20268
Subject(s) - retinoic acid , tbx1 , biology , psychological repression , microbiology and biotechnology , retinoic acid receptor , gene expression , cell culture , genetics , gene , promoter
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.