Vitamin A prevents inner ear defects in mice with congenital homeobox gene deficiency

For the past 75 years, vitamin A and its biologically active metabolites, the retinoids, have been the object of intense study in biology and medicine. A large body of evidence demonstrates that these nutrients are essential for normal development and survival of vertebrate embryos, including mammals. In fact, it has been known since the mid-1930s that vitamin A deficiency during pregnancy results in death of the fetus and congenital abnormalities. Similarly, excess dietary intake of vitamin A can also cause teratogenic responses. Among the main targets of both deficiency and excess retinoid-induced teratogenesis are the heart, limbs, craniofacial structures, central nervous system, and the inner ear. Specific malformations are induced in a stage- and dose-dependent manner. Thus, these studies indicate that precise levels and timing of action of vitamin A metabolites are required for normal patterning of embryonic structures. In addition, the discovery of the nuclear receptors for retinoic acid (RA) and other vitamin A derivatives provided a molecular basis to explain how distinct doses of these compounds elicit cell-specific responses via the direct transcriptional activation of a panel of target genes.