Postgastrulation Smad2-deficient embryos show defects in embryo turning and anterior morphogenesis
Postgastrulation Smad2-deficient embryos show defects in embryo turning and anterior morphogenesis
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DOI：
10.1073/pnas.96.22.12595
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发表时间：
1999-10-26
影响因子：
11.1
通讯作者：
Kucherlapati, R
中科院分区：
文献类型：
--
作者：
Heyer, J;Escalante-Alcalde, D;Kucherlapati, R
SMAD 2是转化生长因子β和激活素信号通路的成员，为了研究Smad 2在原肠胚形成后发育中的作用，我们独立地产生了该基因中具有无效突变的小鼠。Smad 2缺陷型胚胎在妊娠7.5天左右死亡，因为原肠胚形成失败和未能建立前-后（A-P）轴。同源异型盒基因Hex（已知最早的A-P极性标记和预期的头部组织者）的表达被发现在Smad 2缺陷的胚胎中缺失。纯合突变胚胎和胚胎干细胞形成中胚层衍生物，揭示中胚层诱导是SMAD 2独立的。在存在野生型胚外组织的情况下，Smad 2缺陷型胚胎在胚胎发育后7.5天至10.5天发育，表明在胚外组织中需要SMAD 2来产生A-P轴和原肠胚形成。拯救的原肠胚形成后胚胎显示头部结构畸形、异常胚胎转向和独眼畸形。我们的研究结果表明，Smad 2的表达需要在胚胎发生的几个阶段。
SMAD2 is a member of the transforming growth factor beta and activin-signaling pathway, To examine the role of Smad2 in postgastrulation development, we independently generated mice with a null mutation in this gene. Smad2-deficient embryos die around day 7.5 of gestation because of failure of gastrulation and failure to establish an anterior-posterior (A-P) axis. Expression of the homeobox gene Hex (the earliest known marker of the A-P polarity and the prospective head organizer) was found to be missing in Smad2-deficient embryos. Homozygous mutant embryos and embryonic stem cells formed mesoderm derivatives revealing that mesoderm induction is SMAD2 independent. In the presence of wild-type extraembryonic tissues, Smad2-deficient embryos developed beyond 7.5 and up to 10.5 days postcoitum, demonstrating a requirement for SMAD2 in extraembryonic tissues for the generation of an A-P axis and gastrulation, The rescued postgastrulation embryos showed malformation of head structures, abnormal embryo turning, and cyclopia. Our results show that Smad2 expression is required at several stages during embryogenesis.