Tead4 and Tfap2c generate bipotency and a bistable switch in totipotent embryos to promote robust lineage diversification.
Nat Struct Mol Biol
; 31(6): 964-976, 2024 Jun.
Article
em En
| MEDLINE
| ID: mdl-38789684
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
/
Proteínas de Ligação a DNA
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Fator de Transcrição AP-2
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Fatores de Transcrição de Domínio TEA
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Nat Struct Mol Biol
Ano de publicação:
2024
Tipo de documento:
Article