Mouse embryos lacking Smad1 signals display defects in extra-embryonic tissues and germ cell formation.
Mouse embryos lacking Smad1 signals display defects in extra-embryonic tissues and germ cell formation.
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发表时间：
2001-09
期刊：
影响因子：
4.6
通讯作者：
K. Tremblay;N. R. Dunn;E. Robertson
中科院分区：
文献类型：
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作者：
K. Tremblay;N. R. Dunn;E. Robertson
Smad蛋白是分泌生长因子的转化生长因子β（TGF β）家族的重要细胞内介质。Smad 1是由TGF β分子的骨形态发生蛋白（BMP）亚组提供的信号的效应子。为了了解Smad 1在小鼠发育中的作用，我们在ES细胞中使用同源重组产生了Smad 1功能丧失等位基因。smad 1-/-胚胎在10.5 dpc时死亡，因为它们未能连接到胎盘。突变胚胎是第一次识别的7.0 DPC，由于一个特征性的本地化的内脏内胚层在后胚胎/胚外交界处的outpocketing，伴随着显着扭曲的外胚层和新生的中胚层。嵌合体分析表明，这两个缺陷是由于需要Smad 1在胚胎外组织。到7.5 dpc，Smad 1缺陷型胚胎在尿囊形成中表现出明显的损害。相比之下，绒毛膜过度增殖，不规则地折叠在胚胎外空间内，并且在近端迁移中受到阻碍。已知BMP信号对于原始生殖细胞的特化和增殖是必不可少的。我们发现Smad 1缺陷的胚胎中原始生殖细胞急剧减少，这表明Smad 1依赖的信号在原始生殖细胞的规范中起着重要作用。令人惊讶的是，尽管BMP信号在胚胎组织中起着关键作用，但Smad 1缺陷的胚胎发育非常正常。Smad 1，Smad 5和Smad 8在早期小鼠胚胎的表达结构域的检查表明，虽然Smad 1是唯一的内脏内胚层在6.5 dpc的表达，在其他组织中Smad 1与Smad 5和/或Smad 8共表达。总的来说，这些数据揭示了Smad 1信号在协调支持子宫环境内发育所必需的胚外结构生长中的独特功能。
The Smad proteins are important intracellular mediators of the transforming growth factor beta (TGFbeta) family of secreted growth factors. Smad1 is an effector of signals provided by the bone morphogenetic protein (BMP) sub-group of TGFbeta molecules. To understand the role of Smad1 in mouse development, we have generated a Smad1 loss-of-function allele using homologous recombination in ES cells. Smad1-/- embryos die by 10.5 dpc because they fail to connect to the placenta. Mutant embryos are first recognizable by 7.0 dpc, owing to a characteristic localized outpocketing of the visceral endoderm at the posterior embryonic/extra-embryonic junction, accompanied by a dramatic twisting of the epiblast and nascent mesoderm. Chimera analysis reveals that these two defects are attributable to a requirement for Smad1 in the extra-embryonic tissues. By 7.5 dpc, Smad1-deficient embryos show a marked impairment in allantois formation. By contrast, the chorion overproliferates, is erratically folded within the extra-embryonic space and is impeded in proximal migration. BMP signals are known to be essential for the specification and proliferation of primordial germ cells. We find a drastic reduction of primordial germ cells in Smad1-deficient embryos, suggesting an essential role for Smad1-dependent signals in primordial germ cell specification. Surprisingly, despite the key involvement of BMP signaling in tissues of the embryo proper, Smad1-deficient embryos develop remarkably normally. An examination of the expression domains of Smad1, Smad5 and Smad8 in early mouse embryos show that, while Smad1 is uniquely expressed in the visceral endoderm at 6.5 dpc, in other tissues Smad1 is co-expressed with Smad5 and/or Smad8. Collectively, these data have uncovered a unique function for Smad1 signaling in coordinating the growth of extra-embryonic structures necessary to support development within the uterine environment.