Fate specification triggers a positive feedback loop of TEAD-YAP and NANOG to promote epiblast formation in preimplantation embryos

Naoki Hirono; Masakazu Hashimoto; Hiromi Shimojo; Hiroshi Sasaki

doi:10.1242/dev.203091

Fate specification triggers a positive feedback loop of TEAD-YAP and NANOG to promote epiblast formation in preimplantation embryos

Development. 2025 Jan 1;152(1):dev203091. doi: 10.1242/dev.203091. Epub 2025 Jan 9.

Authors

Naoki Hirono¹, Masakazu Hashimoto^{1

2}, Hiromi Shimojo¹, Hiroshi Sasaki¹

Affiliations

¹ Laboratory for Embryogenesis, Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565-0871, Japan.
² Japan Science and Technology Agency, PRESTO, Kawaguchi, Saitama 332-0012, Japan.

PMID: 39629521
DOI: 10.1242/dev.203091

Abstract

In preimplantation embryos, epiblast (EPI) fate specification from the inner cell mass is controlled by the segregation of NANOG and GATA6 expression. TEAD-YAP interaction is activated during EPI formation and is required for pluripotency factor expression. These events occur asynchronously with similar timing during EPI formation, and their relationship remains elusive. Here, we examined the relationship between NANOG-GATA6 and TEAD-YAP. The nuclear accumulation of YAP takes place only in EPI-specified cells, and a positive feedback loop operates between NANOG and TEAD-YAP. The effects of TEAD-YAP on SOX2 upregulation in EPI-specified cells are likely indirect. EPI fate specification also alters the response of Nanog, Sox2 and Cdx2 to TEAD-YAP. These results suggest that EPI-fate specification alters the transcriptional network from the morula-like to the EPI-specified state and activates TEAD-YAP to trigger a positive feedback loop with NANOG, which stabilizes the EPI fate. The coordinated occurrence of these processes in individual cells likely supports proper EPI formation under the condition of asynchronous EPI-fate specification.

Keywords: Epiblast; Mouse; NANOG; Preimplantation embryo; TEAD; YAP.

MeSH terms

Adaptor Proteins, Signal Transducing / genetics
Adaptor Proteins, Signal Transducing / metabolism
Animals
Blastocyst* / cytology
Blastocyst* / metabolism
CDX2 Transcription Factor / genetics
CDX2 Transcription Factor / metabolism
Cell Cycle Proteins / genetics
Cell Cycle Proteins / metabolism
Cell Differentiation
DNA-Binding Proteins / genetics
DNA-Binding Proteins / metabolism
Feedback, Physiological*
Female
GATA6 Transcription Factor / genetics
GATA6 Transcription Factor / metabolism
Gene Expression Regulation, Developmental*
Germ Layers* / cytology
Germ Layers* / metabolism
Mice
Nanog Homeobox Protein* / genetics
Nanog Homeobox Protein* / metabolism
Phosphoproteins / genetics
Phosphoproteins / metabolism
SOXB1 Transcription Factors / genetics
SOXB1 Transcription Factors / metabolism
TEA Domain Transcription Factors / metabolism
Transcription Factors* / genetics
Transcription Factors* / metabolism
YAP-Signaling Proteins* / metabolism

Substances

Nanog Homeobox Protein
YAP-Signaling Proteins
Nanog protein, mouse
Yap1 protein, mouse
Transcription Factors
Adaptor Proteins, Signal Transducing
GATA6 Transcription Factor
SOXB1 Transcription Factors
Gata6 protein, mouse
CDX2 Transcription Factor
Sox2 protein, mouse
Phosphoproteins
Cdx2 protein, mouse
Cell Cycle Proteins
DNA-Binding Proteins
TEA Domain Transcription Factors

Abstract

MeSH terms

Substances

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