| First Author | Nakagawa S | Year | 2024 |
| Journal | Stem Cell Reports | Volume | 19 |
| Issue | 5 | Pages | 689-709 |
| PubMed ID | 38701778 | Mgi Jnum | J:348701 |
| Mgi Id | MGI:7642599 | Doi | 10.1016/j.stemcr.2024.04.004 |
| Citation | Nakagawa S, et al. (2024) The Wnt-dependent master regulator NKX1-2 controls mouse pre-implantation development. Stem Cell Reports 19(5):689-709 |
| abstractText | 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. |
