‘A’ forming experience

Abstract

The stringent guidelines for vitamin A intake during pregnancy have been justified by the identification of a single enzyme that activates the expression of specific target genes throughout the embryo. The enzyme CPY26 metabolizes retinoic acid (RA), an essential derivative of vitamin A. The uneven distribution of this vitamin along the central-body axis of the developing embryo is essential for normal development. Over- or under-dosage of vitamin A during pregnancy results in morphological defects ranging from cranio-facial, cardiac, lung and genito-urinary abnormalities to neurological abnormalities. The level of RA in the embryo is maintained by a delicate balance between RA synthesis and RA degradation. Hiroshi Hamada et al. [Genes Dev. (2001) 15, 213–225] and Martin Petkovich et al. [Genes Dev. (2001) 15, 226–240], performed genetic ablation of murine CYP26, which resulted in elevated RA levels in specific embryonic areas. The mutant mouse embryos were not viable – major defects including spina bifida, truncation of the posterior body and abnormalities of the kidney, brain and vertebrae were seen. CPY26 seems, therefore, to protect the developing embryo from the deleterious effects of excessive RA activity. S. de B.