Nakagawa, ShomaCarnevali, DavideTan, XiangtianAlvarez, Mariano J.Parfitt, David-EmlynDi Vicino, UmbertoArumugam, KarthikShin, WilliamAranda, SergiNormanno, DavideSebastián Pérez, RubénCannatá, ChiaraCortes, PaolaNeguembor, Maria VictoriaShen, Michael M.Califano, AndreaCosma, Maria Pia2024-09-062024-09-062024Nakagawa 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.2024.04.0042213-6711http://hdl.handle.net/10230/61032Embryo 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.application/pdfeng© 2024 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).info:eu-repo/semantics/articlehttp://dx.doi.org/10.1016/j.stemcr.2024.04.004NKX1-2RNA polymerase IWnt signalingEmbryonic stem cellMaster regulator analysisMouse embryoNucleolusRibosome biogenesisSystems biologyinfo:eu-repo/semantics/openAccess