Genetic disruption of CYP26B1 severely affects development of neural crest derived head structures, but does not compromise hindbrain patterning.
Cyp26b1 encodes a cytochrome-P450 enzyme that catabolizes retinoic acid (RA), a vitamin A derived signaling molecule. We have examined Cyp26b1(-/-) mice and report that mutants exhibit numerous abnormalities in cranial neural crest cell derived tissues. At embryonic day (E) 18.5 Cyp26b1(-/-) animals exhibit a truncated mandible, abnormal tooth buds, reduced ossification of calvaria, and are missing structures of the maxilla and nasal process. Some of these abnormalities may be due to defects in formation of Meckel's cartilage, which is truncated with an unfused distal region at E14.5 in mutant animals. Despite the severe malformations, we did not detect any abnormalities in rhombomere segmentation, or in patterning and migration of anterior hindbrain derived neural crest cells. Abnormal migration of neural crest cells toward the posterior branchial arches was observed, which may underlie defects in larynx and hyoid development. These data suggest different periods of sensitivity of anterior and posterior hindbrain neural crest derivatives to elevated levels of RA in the absence of CYP26B1.
Maclean
Glenn
G
Department of Pathology, Division of Cancer Biology and Genetics, Queen's University, Kingston, Ontario, Canada.
Dollé
Pascal
P
Petkovich
Martin
M
D000818:Animals; D019521:Body Patterning; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000196:embryology / Q000201:enzymology; D018507:Gene Expression Regulation, Developmental; D015971:Gene Expression Regulation, Enzymologic; D006257:Head / Q000196:embryology*; D051379:Mice; D009333:Neck / Q000196:embryology; D009432:Neural Crest / Q000196:embryology* / Q000201:enzymology*; D010012:Osteogenesis; D000072516:Retinoic Acid 4-Hydroxylase; D012249:Rhombencephalon / Q000196:embryology / Q000201:enzymology
D003577:Cytochrome P-450 Enzyme System; D000072516:Retinoic Acid 4-Hydroxylase