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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...

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Detalles Bibliográficos
Autores principales: Frum, Tristan, Murphy, Tayler M, Ralston, Amy
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6289571/
https://www.ncbi.nlm.nih.gov/pubmed/30526858
http://dx.doi.org/10.7554/eLife.42298
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author Frum, Tristan
Murphy, Tayler M
Ralston, Amy
author_facet Frum, Tristan
Murphy, Tayler M
Ralston, Amy
author_sort Frum, Tristan
collection PubMed
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.
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spelling pubmed-62895712018-12-13 HIPPO signaling resolves embryonic cell fate conflicts during establishment of pluripotency in vivo Frum, Tristan Murphy, Tayler M Ralston, Amy eLife Developmental Biology 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. eLife Sciences Publications, Ltd 2018-12-11 /pmc/articles/PMC6289571/ /pubmed/30526858 http://dx.doi.org/10.7554/eLife.42298 Text en © 2018, Frum et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Developmental Biology
Frum, Tristan
Murphy, Tayler M
Ralston, Amy
HIPPO signaling resolves embryonic cell fate conflicts during establishment of pluripotency in vivo
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 Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6289571/
https://www.ncbi.nlm.nih.gov/pubmed/30526858
http://dx.doi.org/10.7554/eLife.42298
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