HIPPO signaling resolves embryonic cell fate conflicts during establishment of pluripotency in vivo
During mammalian development, the challenge for the embryo is to override intrinsic cellular plasticity to drive cells to distinct fates. Here, we unveil novel roles for the HIPPO signaling pathway in controlling cell positioning and expression of Sox2, the first marker of pluripotency in the mouse...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2018-12-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/42298 |
| _version_ | 1828376122456276992 |
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| author | Tristan Frum Tayler M Murphy Amy Ralston |
| author_facet | Tristan Frum Tayler M Murphy Amy Ralston |
| author_sort | Tristan Frum |
| collection | DOAJ |
| description | During mammalian development, the challenge for the embryo is to override intrinsic cellular plasticity to drive cells to distinct fates. Here, we unveil novel roles for the HIPPO signaling pathway in controlling cell positioning and expression of Sox2, the first marker of pluripotency in the mouse early embryo. We show that maternal and zygotic YAP1 and WWTR1 repress Sox2 while promoting expression of the trophectoderm gene Cdx2 in parallel. Yet, Sox2 is more sensitive than Cdx2 to Yap1/Wwtr1 dosage, leading cells to a state of conflicted cell fate when YAP1/WWTR1 activity is moderate. Remarkably, HIPPO signaling activity resolves conflicted cell fate by repositioning cells to the interior of the embryo, independent of its role in regulating Sox2 expression. Rather, HIPPO antagonizes apical localization of Par complex components PARD6B and aPKC. Thus, negative feedback between HIPPO and Par complex components ensure robust lineage segregation. |
| first_indexed | 2024-04-14T07:55:10Z |
| format | Article |
| id | doaj.art-d5fa56eaab5e4c5782b7bd75d977e6b1 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-14T07:55:10Z |
| publishDate | 2018-12-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-d5fa56eaab5e4c5782b7bd75d977e6b12022-12-22T02:05:04ZengeLife Sciences Publications LtdeLife2050-084X2018-12-01710.7554/eLife.42298HIPPO signaling resolves embryonic cell fate conflicts during establishment of pluripotency in vivoTristan Frum0https://orcid.org/0000-0003-3452-8762Tayler M Murphy1Amy Ralston2https://orcid.org/0000-0003-3755-8262Department of Biochemistry and Molecular Biology, Michigan State University, Michigan, United StatesGenetics Graduate Program, Michigan State University, Michigan, United States; Reproductive and Developmental Biology Training Program, Michigan State University, Michigan, United StatesDepartment of Biochemistry and Molecular Biology, Michigan State University, Michigan, United States; Genetics Graduate Program, Michigan State University, Michigan, United States; Reproductive and Developmental Biology Training Program, Michigan State University, Michigan, United StatesDuring mammalian development, the challenge for the embryo is to override intrinsic cellular plasticity to drive cells to distinct fates. Here, we unveil novel roles for the HIPPO signaling pathway in controlling cell positioning and expression of Sox2, the first marker of pluripotency in the mouse early embryo. We show that maternal and zygotic YAP1 and WWTR1 repress Sox2 while promoting expression of the trophectoderm gene Cdx2 in parallel. Yet, Sox2 is more sensitive than Cdx2 to Yap1/Wwtr1 dosage, leading cells to a state of conflicted cell fate when YAP1/WWTR1 activity is moderate. Remarkably, HIPPO signaling activity resolves conflicted cell fate by repositioning cells to the interior of the embryo, independent of its role in regulating Sox2 expression. Rather, HIPPO antagonizes apical localization of Par complex components PARD6B and aPKC. Thus, negative feedback between HIPPO and Par complex components ensure robust lineage segregation.https://elifesciences.org/articles/42298pluripotencymammalscell polarity |
| spellingShingle | Tristan Frum Tayler M Murphy Amy Ralston HIPPO signaling resolves embryonic cell fate conflicts during establishment of pluripotency in vivo eLife pluripotency mammals cell polarity |
| title | HIPPO signaling resolves embryonic cell fate conflicts during establishment of pluripotency in vivo |
| title_full | HIPPO signaling resolves embryonic cell fate conflicts during establishment of pluripotency in vivo |
| title_fullStr | HIPPO signaling resolves embryonic cell fate conflicts during establishment of pluripotency in vivo |
| title_full_unstemmed | HIPPO signaling resolves embryonic cell fate conflicts during establishment of pluripotency in vivo |
| title_short | HIPPO signaling resolves embryonic cell fate conflicts during establishment of pluripotency in vivo |
| title_sort | hippo signaling resolves embryonic cell fate conflicts during establishment of pluripotency in vivo |
| topic | pluripotency mammals cell polarity |
| url | https://elifesciences.org/articles/42298 |
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