Dose-dependent Smad1, Smad5 and Smad8 signaling in the early mouse embryo.
Dose-dependent Smad1, Smad5 and Smad8 signaling in the early mouse embryo.
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DOI：
10.1016/j.ydbio.2006.04.442
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发表时间：
2006-08-01
影响因子：
2.7
通讯作者：
Robertson EJ
中科院分区：
文献类型：
--
作者：
Arnold SJ;Maretto S;Islam A;Bikoff EK;Robertson EJ
三种密切相关的哺乳动物R-Smads，即Smad 1，Smad 5和Smad 8，被BMP受体激活。在这里，我们已经采取了遗传方法，以进一步剖析他们可能独特的和/或共享的作用，在早期小鼠发育。创建Smad8.LacZ报告等位基因以可视化Smad 8表达结构域。Smad 8最初仅在内脏卵黄囊（VYS）内胚层中表达，并且在后期阶段在胚胎中表现出高度受限的表达模式。此外，工程化Smad 8条件和无效等位基因。所有等位基因清楚地表明，成人Smad 8纯合突变体是可行的和可育的。为了阐明基因剂量效应，我们操纵三种BMP R-Smads的表达比率。Smad 8纯合子也缺乏一个拷贝的Smad 1或Smad 5没有表现出明显的表型，并在Smad 1或Smad 5无效的胚胎中观察到的组织紊乱在没有Smad 8的情况下并没有加剧。然而，我们发现Smad 1和Smad 5之间存在深刻的遗传相互作用。因此，对于Smad 1和Smad 5突变体胚胎，Smad 1 +/−：Smad 5 +/−双杂合子在E10.5前死亡，并在尿囊形态发生、心脏成环和原始生殖细胞（PGC）特化方面显示缺陷。这些实验首次证明Smad 1和Smad 5的功能合作，以管理BMP靶基因的表达在早期哺乳动物胚胎。
Three closely related mammalian R-Smads, namely Smad1, Smad5 and Smad8, are activated by BMP receptors. Here we have taken a genetic approach to further dissect their possibly unique and/or shared roles during early mouse development. A Smad8.LacZ reporter allele was created to visualize Smad8 expression domains. Smad8 is initially expressed only in the visceral yolk sac (VYS) endoderm and shows a highly restricted pattern of expression in the embryo proper at later stages. In addition, Smad8 conditional and null alleles were engineered. All alleles clearly demonstrate that adult Smad8 homozygous mutants are viable and fertile. To elucidate gene dosage effects, we manipulated expression ratios of the three BMP R-Smads. Smad8 homozygotes also lacking one copy of Smad1 or Smad5 did not exhibit overt phenotypes, and the tissue disturbances seen in Smad1 or Smad5 null embryos were not exacerbated in the absence of Smad8. However, we discovered a profound genetic interaction between Smad1 and Smad5. Thus, as for Smad1 and Smad5 mutant embryos, Smad1 +/− :Smad5 +/− double heterozygotes die by E10.5 and display defects in allantois morphogenesis, cardiac looping and primordial germ cell (PGC) specification. These experiments demonstrate for the first time that Smad1 and Smad5 function cooperatively to govern BMP target gene expression in the early mammalian embryo.
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影响因子：
64.8
作者：
Brennan, J;Lu, CC;Robertson, EJ
通讯作者：
Robertson, EJ
影响因子：
64.8
作者：
Imamura, T;Takase, M;Miyazono, K
通讯作者：
Miyazono, K
影响因子：
2.7
作者：
CSERJESI, P;BROWN, D;OLSON, EN
通讯作者：
OLSON, EN
影响因子：
10.5
作者：
Dunn, NR;Koonce, CH;Robertson, EJ
通讯作者：
Robertson, EJ
影响因子：
4.6
作者：
Chu, GC;Dunn, NR;Robertson, EJ
通讯作者：
Robertson, EJ