BMP antagonism is required in both the node and lateral plate mesoderm for mammalian left-right axis establishment
BMP antagonism is required in both the node and lateral plate mesoderm for mammalian left-right axis establishment
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DOI：
10.1242/dev.018986
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发表时间：
2008-07-15
期刊：
影响因子：
4.6
通讯作者：
Klingensmith, John
中科院分区：
文献类型：
--
作者：
Mine, Naoki;Anderson, Ryan M.;Klingensmith, John
在小鼠中，左右（L-R）模式依赖于节点周围Nodal的不对称表达，导致Nodal特异性地在左侧板中胚层（LPM）中表达。骨形态发生蛋白（BMP）信号也参与其中，但与Nodal表达的机制关系仍不清楚。我们发现，BMP信号转导是较高的，在正确的LPM，虽然Bmp 4，这是所需的L-R图案，对称表达。相比之下，BMP拮抗剂头蛋白（Nog）和腱蛋白（Chrd）在左侧LPM中以更高的水平表达。在Chrd; Nog双突变体中，BMP信号在两侧都升高，而Nodal表达不存在。在双突变体的左LPM中Nog的异位表达恢复Nodal表达。野生型胚胎左侧LPM中异位Bmp 4表达抑制Nodal转录，而右侧LPM中异位Nog导致Nodal表达不当。这些数据表明，腱蛋白和头蛋白的功能，以限制BMP信号在左LPM，从而解抑制Nodal表达。在淋巴结中，它们促进外周Nodal表达和适当的淋巴结形态，可能与Notch信号传导一致。这些结果表明，BMP拮抗作用是必需的，在节点和LPM，以促进L-R轴建立在哺乳动物胚胎。
In mouse, left-right (L-R) patterning depends on asymmetric expression of Nodal around the node, leading to Nodal expression specifically in the left lateral plate mesoderm (LPM). Bone morphogenetic protein (BMP) signaling is also involved, but the mechanistic relationship with Nodal expression remains unclear. We find that BMP signal transduction is higher in the right LPM, although Bmp4, which is required for L-R patterning, is expressed symmetrically. By contrast, the BMP antagonists noggin (Nog) and chordin (Chrd) are expressed at higher levels in the left LPM. In Chrd; Nog double mutants, BMP signaling is elevated on both sides, whereas Nodal expression is absent. Ectopic expression of Nog in the left LPM of double mutants restores Nodal expression. Ectopic Bmp4 expression in the left LPM of wild-type embryos represses Nodal transcription, whereas ectopic Nog in the right LPM leads to inappropriate Nodal expression. These data indicate that chordin and noggin function to limit BMP signaling in the left LPM, thereby derepressing Nodal expression. In the node, they promote peripheral Nodal expression and proper node morphology, potentially in concert with Notch signaling. These results indicate that BMP antagonism is required in both the node and LPM to facilitate L-R axis establishment in the mammalian embryo.