The role of CYP26 enzymes in defining appropriate retinoic acid exposure during embryogenesis.
Retinoic acid (RA) is a pleiotropic derivative of vitamin A, or retinol, which is responsible for all of the bioactivity associated with this vitamin. The teratogenic influences of vitamin A deficiency and excess RA in rodents were first observed more than 50 years ago. Efforts over the last 15-20 years have refined these observations by defining the molecular mechanisms that control RA availability and signaling during murine embryonic development. This review will discuss our current understanding of the role of RA in teratogenesis, with specific emphasis on the essential function of the RA catabolic CYP26 enzymes in preventing teratogenic consequences caused by uncontrolled distribution of RA. Particular focus will be paid to the RA-sensitive tissues of the caudal and cranial regions, the limb, and the testis, and how genetic mutation of factors controlling RA distribution have revealed important roles for RA during embryogenesis.
Pennimpede
Tracie
T
Department of Pathology and Molecular Medicine, Cancer Research Institute, Division of Cancer Biology and Genetics, Queen's University, Kingston, Ontario, Canada.
Cameron
Don A
DA
MacLean
Glenn A
GA
Li
Hui
H
Abu-Abed
Suzan
S
Petkovich
Martin
M
D000818:Animals; D000013:Congenital Abnormalities / Q000196:embryology / Q000201:enzymology* / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D047108:Embryonic Development; D005121:Extremities / Q000196:embryology; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009436:Neural Tube Defects / Q000139:chemically induced / Q000196:embryology / Q000201:enzymology; D011247:Pregnancy; D000072516:Retinoic Acid 4-Hydroxylase; D013723:Teratogens / Q000378:metabolism; D013737:Testis / Q000196:embryology; D014212:Tretinoin / Q000378:metabolism*; D014802:Vitamin A Deficiency / Q000196:embryology / Q000201:enzymology* / Q000378:metabolism
D013723:Teratogens; D014212:Tretinoin; D003577:Cytochrome P-450 Enzyme System; D000072516:Retinoic Acid 4-Hydroxylase