title: The retinoic acid metabolising gene, CYP26B1, patterns the cartilaginous cranial neural crest in zebrafish.
abstract: We have investigated the function of the retinoic acid metabolising enzyme, CYP26B1, by administering an antisense morpholino oligonucleotide to zebrafish embryos. The result was an alteration in the morphology of the embryo in those regions which express the gene, namely an embryo with a smaller head, correspondingly smaller hindbrain rhombomeres and severely reduced numbers of vagal brachiomotor neurons. Most strikingly, these embryos had defective or absent jaw cartilages implying a role for this enzyme in patterning or migration of the neural crest cells which give rise to this tissue type. In order to determine whether this phenotype resembles that of excess retinoic acid or a deficiency of retinoic acid, we compared the jaw defects following retinoic acid treatment or DEAB treatment, the latter being an inhibitor of retinoic acid synthesis. The effects of the inhibitor rather than excess retinoic acid most closely phenocopied the jaw defects seen with the Cyp26B1 morpholino which suggests that, at least in the zebrafish embryo, the action of CYP26B1 in the neural crest may not be simply to catabolise all-trans-RA.
authors.affiliation: Randall Division of Cell and Molecular Biophysics, King's College London, UK.
authors.forename: Susan
authors.initials: S
authors.lastname: Reijntjes
authors.forename: Adam
authors.initials: A
authors.lastname: Rodaway
authors.forename: Malcolm
authors.initials: M
authors.lastname: Maden
mesh_terms: D000818:Animals; D002356:Cartilage / Q000196:embryology / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D016373:DNA, Antisense / Q000235:genetics; D004625:Embryo, Nonmammalian / Q000196:embryology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000378:metabolism; D009046:Motor Neurons / Q000378:metabolism; D009432:Neural Crest / Q000196:embryology* / Q000378:metabolism*; D010641:Phenotype; D000072516:Retinoic Acid 4-Hydroxylase; D012249:Rhombencephalon / Q000196:embryology / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014212:Tretinoin / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology; D015027:Zebrafish / Q000196:embryology* / Q000378:metabolism*; D010128:p-Aminoazobenzene / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D016373:DNA, Antisense; C088334:Distal-less homeobox proteins; D018398:Homeodomain Proteins; D014157:Transcription Factors; C007368:C.I. Solvent Yellow 56; D014212:Tretinoin; D010128:p-Aminoazobenzene; D003577:Cytochrome P-450 Enzyme System; D000072516:Retinoic Acid 4-Hydroxylase