Distinct requirements for extra-embryonic and embryonic bone morphogenetic protein 4 in the formation of the node and primitive streak and coordination of left-right asymmetry in the mouse.
Distinct requirements for extra-embryonic and embryonic bone morphogenetic protein 4 in the formation of the node and primitive streak and coordination of left-right asymmetry in the mouse.
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发表时间：
2002-10
期刊：
影响因子：
4.6
通讯作者：
Takeshi Fujiwara;D. B. Dehart;K. Sulik;B. Hogan
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文献类型：
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作者：
Takeshi Fujiwara;D. B. Dehart;K. Sulik;B. Hogan
在小鼠和鸡胚胎中，该节点在产生左右（LR）位置信息中起着核心作用。使用几种不同的策略，我们在小鼠中提供了证据，证明骨形态发生蛋白4 （Bmp4）在两个不同的位点独立地用于节点形态发生和LR模式。Bmp4在滋养细胞衍生的胚外胚层中的表达对于淋巴结和原始条纹的正常形成至关重要。然而，四倍体嵌合体分析表明，即使在恢复正常淋巴结形态的情况下，在上皮细胞来源的组织中制造的Bmp4也是强健的LR模式所必需的。在缺乏胚胎Bmp4的情况下，左侧决定因子如Nodal和Lefty2在左侧外侧板中胚层（LPM）中不表达。在培养的野生型胚胎中，noggin介导的Bmp活性抑制导致LPM中Nodal表达的抑制。因此，与之前在鸡胚中提出的Bmp4抑制左侧基因表达的模型不同，我们的研究结果表明，Bmp作为左侧分子级联的积极促进者，是左侧LPM中节点诱导和维持所必需的。
In the mouse and chick embryo, the node plays a central role in generating left-right (LR) positional information. Using several different strategies, we provide evidence in the mouse that bone morphogenetic protein 4 (Bmp4) is required independently in two different sites for node morphogenesis and for LR patterning. Bmp4 expression in the trophoblast-derived extra-embryonic ectoderm is essential for the normal formation of the node and primitive streak. However, tetraploid chimera analysis demonstrates that Bmp4 made in epiblast-derived tissues is required for robust LR patterning, even when normal node morphology is restored. In the absence of embryonic Bmp4, the expression of left-side determinants such as Nodal and Lefty2 is absent in the left lateral plate mesoderm (LPM). Noggin-mediated inhibition of Bmp activity in cultured wild-type embryos results in suppression of Nodal expression in the LPM. Thus, unlike previous models proposed in the chick embryo in which Bmp4 suppresses left-sided gene expression, our results suggest that Bmp acts as a positive facilitator of the left-sided molecular cascade and is required for Nodal induction and maintenance in the left LPM.