PT  - JOURNAL ARTICLE
AU  - Masakazu Hashimoto
AU  - Hiroshi Sasaki
TI  - Epiblast formation by Tead-Yap-dependent expression of pluripotency factors and competitive elimination of unspecified cells
AID  - 10.1101/449397
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 449397
4099  - http://biorxiv.org/content/early/2018/10/21/449397.short
4100  - http://biorxiv.org/content/early/2018/10/21/449397.full
AB  - The epiblast is a pluripotent cell population first formed in preimplantation embryos and its quality is important for proper development. Here, we examined the mechanisms of epiblast formation and found that the Hippo pathway transcription factor Tead and its coactivator Yap regulate expression of pluripotency factors. After specification of the inner cell mass, Yap accumulates in the nuclei and activates Tead. Tead activity is required for strong expression of pluripotency factors and is variable in the forming epiblast. Cells showing low Tead activity are eliminated from the epiblast through cell competition. Pluripotency factor expression and Myc control cell competition downstream of Tead activity. Cell competition eliminates unspecified cells and is required for proper organization of the epiblast. These results suggest that induction of pluripotency factors by Tead activity and elimination of unspecified cells via cell competition ensure the production of an epiblast with naïve pluripotency.