Removal of maternal retinoic acid by embryonic CYP26 is required for correct Nodal expression during early embryonic patterning
Removal of maternal retinoic acid by embryonic CYP26 is required for correct Nodal expression during early embryonic patterning
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DOI：
10.1101/gad.1776209
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发表时间：
2009-07-15
影响因子：
10.5
通讯作者：
Hamada, Hiroshi
中科院分区：
文献类型：
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作者：
Uehara, Masayuki;Yashiro, Kenta;Hamada, Hiroshi
视黄酸（RA）的丰度取决于其通过视黄醇脱氢酶（RALDH）的合成与其通过CYP 26的降解之间的平衡。特别是，三个CYP26基因的动态表达控制着体内RA的区域水平。催乳前小鼠胚胎表达CYP26，但不表达RALDH。我们现在表明，缺乏所有三个CYP26基因的小鼠表现出体轴的重复，这是由于Nodal表达结构域在整个上胚层中的扩增。发现小鼠Nodal在内含子1中含有在哺乳动物中高度保守的RA响应元件。在缺乏CYP 26的情况下，母源性RA通过该元件激活原肠胚形成前胚胎的整个上胚层中的Nodal表达。这些观察结果表明，母体RA必须通过胚胎CYP 26去除，以在胚胎图案形成期间正确表达Nodal。
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.