Journal article
Tead4 and Tfap2c generate bipotency and a bistable switch in totipotent embryos to promote robust lineage diversification
- Abstract:
- The mouse and human embryo gradually loses totipotency before diversifying into the inner cell mass (ICM, future organism) and trophectoderm (TE, future placenta). The transcription factors TFAP2C and TEAD4 with activated RHOA accelerate embryo polarization. Here we show that these factors also accelerate the loss of totipotency. TFAP2C and TEAD4 paradoxically promote and inhibit Hippo signaling before lineage diversification: they drive expression of multiple Hippo regulators while also promoting apical domain formation, which inactivates Hippo. Each factor activates TE specifiers in bipotent cells, while TFAP2C also activates specifiers of the ICM fate. Asymmetric segregation of the apical domain reconciles the opposing regulation of Hippo signaling into Hippo OFF and the TE fate, or Hippo ON and the ICM fate. We propose that the bistable switch established by TFAP2C and TEAD4 is exploited to trigger robust lineage diversification in the developing embryo.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 6.6MB, Terms of use)
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- Publisher copy:
- 10.1038/s41594-024-01311-9
Authors
+ Eunice Kennedy Shriver National Institute of Child Health and Human Development
More from this funder
- Funder identifier:
- https://ror.org/04byxyr05
- Publisher:
- Springer Nature
- Journal:
- Nature Structural & Molecular Biology More from this journal
- Volume:
- 31
- Issue:
- 6
- Pages:
- 964–976
- Place of publication:
- United States
- Publication date:
- 2024-05-24
- Acceptance date:
- 2024-04-09
- DOI:
- EISSN:
-
1545-9985
- ISSN:
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1545-9993
- Pmid:
-
38789684
- Language:
-
English
- Keywords:
- Pubs id:
-
1999790
- Local pid:
-
pubs:1999790
- Deposit date:
-
2024-05-28
- ARK identifier:
Terms of use
- Copyright holder:
- Zhu et al.
- Copyright date:
- 2024
- Rights statement:
- © 2024, The Author(s). Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.
- Licence:
- CC Attribution (CC BY)
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