Antagonism between Smad1 and Smad2 signaling determines the site of distal visceral endoderm formation in the mouse embryo.
Antagonism between Smad1 and Smad2 signaling determines the site of distal visceral endoderm formation in the mouse embryo.
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DOI：
10.1083/jcb.200808044
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发表时间：
2009-01-26
期刊：
影响因子：
--
通讯作者：
Hamada H
中科院分区：
文献类型：
--
作者：
Yamamoto M;Beppu H;Takaoka K;Meno C;Li E;Miyazono K;Hamada H
小鼠胚胎的前-后轴是通过远端内脏内胚层（DVE）的形成及其随后的迁移而建立的。然而，DVE形成的确切机制仍然未知。在这里，我们表明，骨形态发生蛋白（BMP）信号在DVE形成中起着双重作用。BMP信号传导在早期阶段是原始内胚层分化成胚胎内脏内胚层（VE）所必需的，而在后期阶段，它抑制DVE形成，将其限制在远端区域。Smad 2激活因子如激活素也通过产生对Smad 2信号呈阳性而对Smad 1信号呈阴性的VE区域来促进DVE形成。因此，DVE形成于胚胎的远端，这是VE中唯一的Smad 1信号阴性和Smad 2信号阳性的区域。VE中磷酸化Smad 1和磷酸化Smad 2的水平之间呈反比关系，表明Smad 1和Smad 2介导的信号转导之间存在拮抗作用。
The anterior–posterior axis of the mouse embryo is established by formation of distal visceral endoderm (DVE) and its subsequent migration. The precise mechanism of DVE formation has remained unknown, however. Here we show that bone morphogenetic protein (BMP) signaling plays dual roles in DVE formation. BMP signaling is required at an early stage for differentiation of the primitive endoderm into the embryonic visceral endoderm (VE), whereas it inhibits DVE formation, restricting it to the distal region, at a later stage. A Smad2-activating factor such as Activin also contributes to DVE formation by generating a region of VE positive for the Smad2 signal and negative for Smad1 signal. DVE is thus formed at the distal end of the embryo, the only region of VE negative for the Smad1 signal and positive for Smad2 signal. An inverse relation between the level of phosphorylated Smad1 and that of phosphorylated Smad2 in VE suggests an involvement of antagonism between Smad1- and Smad2-mediated signaling.
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