The ability of the oxidated retinoids to inhibit cellular proliferation is exemplified by their use as chemotherapeutic agents. Exposure of pregnant women to the oxidated retinoids can have deleterious effects on the normal development of the embryo. One abnormality that has been reported in humans is a wide cleft of the secondary palate. In pregnant mice treated with teratogenic doses of retinoic acid (RA) on gestational day 11, 100 percent of the offspring manifest a cleft palate.
The effects of retinoids, both endogenously and exogenously, are primarily mediated by the retinoic acid receptor (RAR) and retinoid X receptor (RXR) transcription factors.
The data presented herein suggest that the retinoid signaling pathway may be involved in both normal growth and RA induced alterations in the growth of the mammalian secondary palate and that this signaling pathway can affect the expression of key cell cycle regulatory molecules. My study provides an initial characterization of RAR, RXR and COUP-TF expression levels during palatogenesis. It also begins to address the effects of retinoic acid on the expression of specific cell cycle regulatory molecules. (Abstract shortened by UMI.)
