%0 Journal Article
%T The Wnt-dependent master regulator NKX1-2 controls mouse pre-implantation development.
%A Nakagawa S
%A Carnevali D
%A Tan X
%A Alvarez MJ
%A Parfitt DE
%A Di Vicino U
%A Arumugam K
%A Shin W
%A Aranda S
%A Normanno D
%A Sebastian-Perez R
%A Cannatá C
%A Cortes P
%A Neguembor MV
%A Shen MM
%A Califano A
%A Cosma MP
%J Stem Cell Reports
%V 19
%N 5
%D 2024 May 14
%M 38701778
%F 7.294
%R 10.1016/j.stemcr.2024.04.004
%X 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.