{"doi":"10.1016/j.stemcr.2024.04.004","title":"The Wnt-dependent master regulator NKX1-2 controls mouse pre-implantation development","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.","journal":"Stem Cell Reports","year":2024,"id":475704,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9561,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":477251,"name":"Davide Carnevali","orcid":"0000-0002-7928-9956","position":1,"is_corresponding":false},{"id":478150,"name":"Xiangtian Tan","orcid":null,"position":2,"is_corresponding":false},{"id":347862,"name":"Mariano J. Alvarez","orcid":"0000-0002-7503-2491","position":3,"is_corresponding":false},{"id":1313017,"name":"David-Emlyn Parfitt","orcid":null,"position":4,"is_corresponding":false},{"id":1312666,"name":"Umberto Di Vicino","orcid":"0000-0001-5209-0982","position":5,"is_corresponding":false},{"id":477249,"name":"K. Arumugam","orcid":"0000-0001-5204-2331","position":6,"is_corresponding":false},{"id":478146,"name":"William Shin","orcid":null,"position":7,"is_corresponding":false},{"id":1312667,"name":"Sergi Aranda","orcid":"0000-0003-3853-430X","position":8,"is_corresponding":false},{"id":186627,"name":"Davide Normanno","orcid":"0000-0003-4740-5542","position":9,"is_corresponding":false},{"id":633934,"name":"Rubén Sebastián-Pérez","orcid":"0000-0001-7209-7612","position":10,"is_corresponding":false},{"id":1312668,"name":"Chiara Cannatá","orcid":"0000-0003-4807-4669","position":11,"is_corresponding":false},{"id":1312669,"name":"Paola Cortes","orcid":"0000-0002-8033-7994","position":12,"is_corresponding":false},{"id":633929,"name":"Maria Victoria Neguembor","orcid":"0000-0002-1583-1304","position":13,"is_corresponding":false},{"id":261873,"name":"Michael M. Shen","orcid":"0000-0002-4042-1657","position":14,"is_corresponding":false},{"id":19046,"name":"Andrea Califano","orcid":"0000-0003-4742-3679","position":15,"is_corresponding":false},{"id":477253,"name":"Maria Pia Cosma","orcid":"0000-0003-4207-5097","position":16,"is_corresponding":false},{"id":1312665,"name":"Shoma Nakagawa","orcid":"0000-0002-7766-613X","position":0,"is_corresponding":true}],"reference_count":80,"raw_metadata":null,"created_at":"2026-07-19T02:06:21.071690Z","pmid":"38701778","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}