Retinoic-acid signalling in node ectoderm and posterior neural plate directs left-right patterning of somitic mesoderm
Retinoic-acid signalling in node ectoderm and posterior neural plate directs left-right patterning of somitic mesoderm
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DOI：
10.1038/ncb1374
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发表时间：
2006-03-01
影响因子：
21.3
通讯作者：
Duester, G
中科院分区：
文献类型：
--
作者：
Sirbu, IO;Duester, G
躯体发生需要轴旁中胚层沿着前后轴沿着进行双侧节律性分割（1）。体节分割的位置取决于前方视黄酸（由视黄醇脱氢酶-2; Raldh 2产生）和后方成纤维细胞生长因子（FGF;由Fgf 8产生）的相反信号梯度（2，3）。视黄酸缺乏的胚胎表现出体节左右不对称（4-6），但目前仍不清楚视黄酸是如何介导左右模式的。在这里，我们表明，视黄酸信号是均匀的左右轴，发生在节点外胚层，但不是节点中胚层。在Raldh 2（-/-）小鼠胚胎中，外胚层Fgf 8表达向前侵入结节外胚层和神经板，但其在体前中胚层中的表达最初不变。在Raldh 2（-/-）小鼠胚胎中，当母体饮食补充有视黄酸直到仅6体节阶段时，挽救了体节发生的晚期阶段，表明仅在节阶段期间需要视黄酸。标记母体视黄酸在拯救的Raldh 2（-/-）胚胎中的作用的视黄酸报告转基因显示，在体节发生过程中视黄酸信号传导的靶点是节外胚层和后神经板，而不是体前中胚层。我们的研究结果表明，拮抗FGF 8的表达，视黄酸发生在外胚层，这种机制的失败产生过多的FGF 8信号到相邻的中胚层，导致最初在较小的体节，然后左右不对称。
Somitogenesis requires bilateral rhythmic segmentation of paraxial mesoderm along the antero-posterior axis(1). The location of somite segmentation depends on opposing signalling gradients of retinoic acid (generated by retinaldehyde dehydrogenase-2; Raldh2) anteriorly and fibroblast growth factor (FGF; generated by Fgf8) posteriorly(2,3). Retinoic-acid-deficient embryos exhibit somite left-right asymmetry(4-6), but it remains unclear how retinoic acid mediates left-right patterning. Here, we demonstrate that retinoic-acid signalling is uniform across the left-right axis and occurs in node ectoderm but not node mesoderm. In Raldh2(-/-) mouse embryos, ectodermal Fgf8 expression encroaches anteriorly into node ectoderm and neural plate, but its expression in presomitic mesoderm is initially unchanged. The late stages of somitogenesis were rescued in Raldh2(-/-) mouse embryos when the maternal diet was supplemented with retinoic acid until only the 6-somite stage, demonstrating that retinoic acid is only needed during node stages. A retinoic-acid-reporter transgene marking the action of maternal retinoic acid in rescued Raldh2(-/-) embryos revealed that the targets of retinoic-acid signalling during somitogenesis are the node ectoderm and the posterior neural plate, not the presomitic mesoderm. Our findings suggest that antagonism of Fgf8 expression by retinoic acid occurs in the ectoderm and that failure of this mechanism generates excessive FGF8 signalling to adjacent mesoderm, resulting initially in smaller somites and then left-right asymmetry.