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.
Footnotes
Author contributions
Conceptualization: N.H., H. Sasaki; Methodology: N.H., M.H., H. Shimojo, H. Sasaki; Software: N.H., H. Sasaki; Validation: N.H., H. Sasaki; Formal analysis: N.H.; Investigation: N.H.; Resources: M.H.; Data curation: N.H., H. Sasaki; Writing - original draft: N.H., H. Sasaki; Writing - review & editing: M.H., H. Shimojo, H. Sasaki; Visualization: N.H.; Supervision: M.H., H. Shimojo, H. Sasaki; Project administration: H. Sasaki; Funding acquisition: N.H., M.H., H. Shimojo, H. Sasaki.
Funding
This work was supported by Japan Society for the Promotion of Science KAKENHI (grant numbers JP19H04778, JP20H03261 and JP21H05288 to H. Sasaki; JP20H05366 and JP22H04673 to M.H.; and JP18K06254 and JP23K05782 to H. Shimojo), Japan Science and Technology Agency PRESTO (grant number JPMJPR1948 to M.H.), and Japan Science and Technology Agency SPRING (grant number JPMJSP2138 to H.N.).
Data availability
The original image data and quantification data for Figs 1A-C and 4A-E are available from the SSBD bioimaging database under accession number ssbd-repos-000399.
