Mst1 and mst2 are essential regulators of trophoblast differentiation and placenta morphogenesis.
Mst1 and mst2 are essential regulators of trophoblast differentiation and placenta morphogenesis.
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Mst1 和 Mst2 是滋养层分化和胎盘形态发生的重要调节因子
DOI：
10.1371/journal.pone.0090701
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Tao W
中科院分区：
文献类型：
--
作者：
Du X;Dong Y;Shi H;Li J;Kong S;Shi D;Sun LV;Xu T;Deng K;Tao W
胎盘对于胎儿的生存和成长是必不可少的，因为它促进了母体循环中营养物质和氧气的输送，以及胎儿排泄物的处理。Mst1和Mst2(Mst1/2)是哺乳动物hpo/MST信号通路的关键组成部分，编码两个高度保守的Ser/Thr激酶，在预防肿瘤的发生和自身免疫、控制T细胞的发育和运输以及胚胎发育中发挥重要作用。然而，它们在胎盘发育中的作用还不完全清楚，潜在的细胞和分子机制仍然难以捉摸。在这里，我们使用常规和条件性(内皮)Mst1/2双基因敲除小鼠来研究Mst1/2在小鼠胎盘发育中的作用。我们发现，在Mst1/2缺陷胎盘中，滋养层巨细胞数量显著增加，而海绵状滋养层细胞几乎完全消失。我们发现Mst1/2缺陷下调了Mash2的表达，而Mash2是抑制滋养层巨细胞分化所必需的。此外，我们发现Mst1/2的内皮特异性缺失导致胎盘迷路血管受损和胚胎致死，但不影响卵黄囊和胚胎本身的血管系统，也不影响心内膜的发育。综上所述，我们的研究结果表明，Mst1/2在妊娠中期通过控制滋养层细胞分化和迷路血管来调控胎盘发育，而Mst1/2通过滋养层和胎儿内皮依赖的方式控制迷路的形态发生。因此，我们的研究确定了Mst1/2在小鼠胎盘发育中的新角色。
The placenta is essential for survival and growth of the fetus because it promotes the delivery of nutrients and oxygen from the maternal circulation as well as fetal waste disposal. Mst1 and Mst2 (Mst1/2), key components of the mammalian hpo/Mst signaling pathway, encode two highly conserved Ser/Thr kinases and play important roles in the prevention of tumorigenesis and autoimmunity, control of T cell development and trafficking, and embryonic development. However, their functions in placental development are not fully understood, and the underlying cellular and molecular mechanisms remain elusive. Here, we investigated the functions of Mst1/2 in mouse placental development using both conventional and conditional (endothelial) Mst1/2 double knockout mice. We found that the number of trophoblast giant cells dramatically increased while spongiotrophoblast cells almost completely disappeared in Mst1/2 deficient placentas. We showed that Mst1/2 deficiency down regulated the expression of Mash2, which is required for suppressing the differentiation of trophoblast giant cells. Furthermore, we demonstrated that endothelial-specific deletion of Mst1/2 led to impaired placental labyrinthine vasculature and embryonic lethality at E11.5, but neither affected vasculature in yolk sac and embryo proper nor endocardium development. Collectively, our findings suggest that Mst1/2 regulate placental development by control of trophoblast cell differentiation and labyrinthine vasculature at midgestation and Mst1/2 control labyrinth morphogenesis in trophoblast- and fetal endothelial-dependent manners. Thus, our studies have defined novel roles of Mst1/2 in mouse placental development.
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DOI：
10.1126/science.1199010
发表时间：
2011-04-22
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Heallen T;Zhang M;Wang J;Bonilla-Claudio M;Klysik E;Johnson RL;Martin JF
通讯作者：
Martin JF
影响因子：
5.3
作者：
Schreiber, J;Riethmacher-Sonnenberg, E;Wegner, M
通讯作者：
Wegner, M
影响因子：
5.3
作者：
Oh, Sangphil;Lee, Dongjun;Lim, Dae-Sik
通讯作者：
Lim, Dae-Sik
影响因子：
3.8
作者：
Cross, JC
通讯作者：
Cross, JC
DOI：
10.1084/jem.20111692
发表时间：
2012-04-09
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Mou F;Praskova M;Xia F;Van Buren D;Hock H;Avruch J;Zhou D
通讯作者：
Zhou D