The Wnt-dependent master regulator NKX1-2 controls mouse pre-implantation development.
Stem Cell Reports
; 19(5): 689-709, 2024 May 14.
Article
em En
| MEDLINE
| ID: mdl-38701778
ABSTRACT
Embryo size, specification, and homeostasis are regulated by a complex gene regulatory and signaling network. Here we used gene expression signatures of Wnt-activated mouse embryonic stem cell (mESC) clones to reverse engineer an mESC regulatory network. We identify NKX1-2 as a novel master regulator of preimplantation embryo development. We find that Nkx1-2 inhibition reduces nascent RNA synthesis, downregulates genes controlling ribosome biogenesis, RNA translation, and transport, and induces severe alteration of nucleolus structure, resulting in the exclusion of RNA polymerase I from nucleoli. In turn, NKX1-2 loss of function leads to chromosome missegregation in the 2- to 4-cell embryo stages, severe decrease in blastomere numbers, alterations of tight junctions (TJs), and impairment of microlumen coarsening. Overall, these changes impair the blastocoel expansion-collapse cycle and embryo cavitation, leading to altered lineage specification and developmental arrest.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
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Proteínas de Homeodomínio
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Regulação da Expressão Gênica no Desenvolvimento
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Desenvolvimento Embrionário
Limite:
Animals
Idioma:
En
Revista:
Stem Cell Reports
Ano de publicação:
2024
Tipo de documento:
Article