Mst1 and mst2 are essential regulators of trophoblast differentiation and placenta morphogenesis.
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/Th...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3942462?pdf=render |
| _version_ | 1818958353740595200 |
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| author | Xingrong Du Yongli Dong Hao Shi Jiang Li Shanshan Kong Donghua Shi Ling V Sun Tian Xu Kejing Deng Wufan Tao |
| author_facet | Xingrong Du Yongli Dong Hao Shi Jiang Li Shanshan Kong Donghua Shi Ling V Sun Tian Xu Kejing Deng Wufan Tao |
| author_sort | Xingrong Du |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-20T11:24:24Z |
| format | Article |
| id | doaj.art-b85def6a92ea4e90a44bbd17ed44bbea |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-20T11:24:24Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-b85def6a92ea4e90a44bbd17ed44bbea2022-12-21T19:42:25ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0193e9070110.1371/journal.pone.0090701Mst1 and mst2 are essential regulators of trophoblast differentiation and placenta morphogenesis.Xingrong DuYongli DongHao ShiJiang LiShanshan KongDonghua ShiLing V SunTian XuKejing DengWufan TaoThe 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.http://europepmc.org/articles/PMC3942462?pdf=render |
| spellingShingle | Xingrong Du Yongli Dong Hao Shi Jiang Li Shanshan Kong Donghua Shi Ling V Sun Tian Xu Kejing Deng Wufan Tao Mst1 and mst2 are essential regulators of trophoblast differentiation and placenta morphogenesis. PLoS ONE |
| title | Mst1 and mst2 are essential regulators of trophoblast differentiation and placenta morphogenesis. |
| title_full | Mst1 and mst2 are essential regulators of trophoblast differentiation and placenta morphogenesis. |
| title_fullStr | Mst1 and mst2 are essential regulators of trophoblast differentiation and placenta morphogenesis. |
| title_full_unstemmed | Mst1 and mst2 are essential regulators of trophoblast differentiation and placenta morphogenesis. |
| title_short | Mst1 and mst2 are essential regulators of trophoblast differentiation and placenta morphogenesis. |
| title_sort | mst1 and mst2 are essential regulators of trophoblast differentiation and placenta morphogenesis |
| url | http://europepmc.org/articles/PMC3942462?pdf=render |
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