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.
Pasqualetti
M
M
Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, Collège de France, C.U. de Strasbourg, Fance.
Rijli
F M
FM
D000818:Animals; D004305:Dose-Response Relationship, Drug; D007758:Ear, Inner / Q000002:abnormalities / Q000187:drug effects*; D005314:Embryonic and Fetal Development / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D005260:Female; D005315:Fetal Diseases / Q000235:genetics / Q000517:prevention & control*; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D011247:Pregnancy; D014157:Transcription Factors / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D014212:Tretinoin / Q000502:physiology / Q000627:therapeutic use*; D000099261:Homeobox A1 Protein
D018398:Homeodomain Proteins; D014157:Transcription Factors; D014212:Tretinoin; D000099261:Homeobox A1 Protein