Dataset Information
Retinoic acid drives aryl hydrocarbon receptor expression and is instrumental to dioxin-induced toxicity during palate development.
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ABSTRACT: Background
Palate development depends on complex events and is very sensitive to disruption. Accordingly, clefts are the most common congenital malformations worldwide, and a connection is proposed with fetal exposure to toxic factors or environmental contaminants, such as dioxins. There is increasing evidence that dioxin interferes with all-trans-retinoic acid (atRA), a hormone-like signal derived from vitamin A, which plays an essential role during embryonic development. Although similarities have been described between dioxin-induced toxicity and the outcome of altered atRA signaling during palate development, their relationship needs to be clarified.Objectives
We used a genetic approach to understand the interaction between atRA and dioxin and to identify the cell type targeted by dioxin toxicity during secondary palate formation in mice.Methods
We analyzed the phenotype of mouse embryos harboring an atRA-sensitive reporter transgene or bearing null mutations for atRA-synthesizing enzymes (RALDH) or atRA receptors (RAR) and maternally exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) at gestation day 10.5.Results
We found that an intact atRA signal was required to enable TCDD to induce cleft palate. This mandatory atRA signal was generated through the activity of RALDH3 in the nasal epithelium and was transduced by RAR? (RARG) in the nasal mesenchyme, where it notably controlled aryl hydrocarbon receptor (Ahr) transcript levels. TCDD also did not alter the developmental pattern of atRA signaling during palate formation.Conclusions
TCDD-induced alteration of secondary palate development in the mouse appears to depend on atRA signaling, which controls AHR expression. This mechanism is likely conserved throughout vertebrate evolution and may therefore be relevant in humans.
SUBMITTER: Jacobs H
PROVIDER: S-EPMC3226489 | biostudies-literature | 2011 Nov
REPOSITORIES: biostudies-literature
Publications
Retinoic acid drives aryl hydrocarbon receptor expression and is instrumental to dioxin-induced toxicity during palate development.
Environmental health perspectives 20110801 11
<h4>Background</h4>Palate development depends on complex events and is very sensitive to disruption. Accordingly, clefts are the most common congenital malformations worldwide, and a connection is proposed with fetal exposure to toxic factors or environmental contaminants, such as dioxins. There is increasing evidence that dioxin interferes with all-trans-retinoic acid (atRA), a hormone-like signal derived from vitamin A, which plays an essential role during embryonic development. Although simil ...[more]
