title: Removal of maternal retinoic acid by embryonic CYP26 is required for correct Nodal expression during early embryonic patterning.
abstract: The abundance of retinoic acid (RA) is determined by the balance between its synthesis by retinaldehyde dehydrogenase (RALDH) and its degradation by CYP26. In particular, the dynamic expression of three CYP26 genes controls the regional level of RA within the body. Pregastrulation mouse embryos express CYP26 but not RALDH. We now show that mice lacking all three CYP26 genes manifest duplication of the body axis as a result of expansion of the Nodal expression domain throughout the epiblast. Mouse Nodal was found to contain an RA-responsive element in intron 1 that is highly conserved among mammals. In the absence of CYP26, maternally derived RA activates Nodal expression in the entire epiblast of pregastrulation embryos via this element. These observations suggest that maternal RA must be removed by embryonic CYP26 for correct Nodal expression during embryonic patterning.
authors: Developmental Genetics Group, Graduate School of Frontier Biosciences, Osaka University, Osaka, Japan.
authors: Masayuki
authors: M
authors: Uehara
authors: Kenta
authors: K
authors: Yashiro
authors: Katsuyoshi
authors: K
authors: Takaoka
authors: Masamichi
authors: M
authors: Yamamoto
authors: Hiroshi
authors: H
authors: Hamada
mesh_terms: D000818:Animals; D001483:Base Sequence; D019521:Body Patterning / Q000502:physiology*; D017124:Conserved Sequence; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D005855:Germ Layers / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D055457:Nodal Protein / Q000235:genetics / Q000378:metabolism*; D010802:Phylogeny; D000072516:Retinoic Acid 4-Hydroxylase; D016415:Sequence Alignment; D015398:Signal Transduction; D013997:Time Factors; D014212:Tretinoin / Q000378:metabolism*
chemical_list: D055457:Nodal Protein; C526008:Nodal protein, mouse; D014212:Tretinoin; D003577:Cytochrome P-450 Enzyme System; D000072516:Retinoic Acid 4-Hydroxylase