{Reference Type}: Journal Article
{Title}: The Wnt-dependent master regulator NKX1-2 controls mouse pre-implantation development.
{Author}: Nakagawa S;Carnevali D;Tan X;Alvarez MJ;Parfitt DE;Di Vicino U;Arumugam K;Shin W;Aranda S;Normanno D;Sebastian-Perez R;Cannatá C;Cortes P;Neguembor MV;Shen MM;Califano A;Cosma MP;
{Journal}: Stem Cell Reports
{Volume}: 19
{Issue}: 5
{Year}: 2024 May 14
{Factor}: 7.294
{DOI}: 10.1016/j.stemcr.2024.04.004
{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.