Figure 1: Regions in the mouse embryo which are responsive to retinoic acid. The picture on the left represents a 11.5 day embryo with staining in the forebrain and frontonasal region. The picture on the right is a 14.5 day embryo with staining in the jaw, optic region, whisker pads, and between the digits in the hand (Gilbert, 1994).
A metabolite of vitamin A, retinoic acid has been used commercially under the name Accutane, a type of medication which can treat cystic acne. Because vitamin A has been known to cause deformities in developing animals since the 1950s, warning labels were placed on the medicine to warn pregnant women from using the medicine. Pregnant woman using Accutane have had fetuses born with various kinds of congenital defects, including defective or missing ears, jaws, and cleft palate and abnormalities to the thymic system, aortic arch, and the central nervous system. This abnormal fetal development occurs due to an excessive amount of retinoids in the fetus. If a mother eats a diet low in vitamin A, the fetus will also develop abnormally. A balanced amount of retinoids is thus necessary for the development of a normal fetus.
While the teratogenic effects of retinoic acid have been known for some time, only recently have we discovered the details of the mechanisms underlying how retinoic acid affects embryonic development. The types of abnormalities caused by retinoic acid are thought to result from its ability to change the expression of certain Hox genes which thus respecifies structures along the anterior-posterior axis and inhibits neural crest cell migration out of the neural tube in the cranial region. Retinoic acid regulates the expression of the homeotic gene complex in many organisms; these genes have been evolutionarily conserved beginning with Drosophila. Homeotic genes pattern embryonic development by establishing a coordinate system throughout the embryo. These genes have highly conserved DNA binding domains which are regions that bind to DNA. Since they usually function as a unit, a group of homeotic proteins are commonly referred to as Hox complexes in mammals. This complex is equivalent to each of the HOM complexes (Antennapedia and bithorax complex). Both pattern the developing body axis with similar expression patterns. This paper reviews the literature concerning the function of retinoic acid in pattern development by regulating the expression of the Hox complex.