The Wnt-dependent master regulator NKX1-2 controls mouse pre-implantation development
The Wnt-dependent master regulator NKX1-2 controls mouse pre-implantation development
Citació
- Nakagawa S, Carnevali D, Tan X, Alvarez MJ, Parfitt DE, Di Vicino U, et al. The Wnt-dependent master regulator NKX1-2 controls mouse pre-implantation development. Stem Cell Reports. 2024 May 14;19(5):689-709. DOI: 10.1016/j.stemcr.2024.04.004
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Descripció
Resum
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.