Removal of maternal retinoic acid by embryonic CYP26 is required for correct Nodal expression during early embryonic patterning.
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.
Uehara
Masayuki
M
Developmental Genetics Group, Graduate School of Frontier Biosciences, Osaka University, Osaka, Japan.
Yashiro
Kenta
K
Takaoka
Katsuyoshi
K
Yamamoto
Masamichi
M
Hamada
Hiroshi
H
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*
D055457:Nodal Protein; C526008:Nodal protein, mouse; D014212:Tretinoin; D003577:Cytochrome P-450 Enzyme System; D000072516:Retinoic Acid 4-Hydroxylase