{"doi":"10.1073/pnas.2421772122","title":"Double assurance in the induction of axial development by egg dorsal determinants in <i>Xenopus</i> embryos","abstract":"We recently reported that microinjection of Xenopus nodal-related ( xnr ) mRNAs into β-catenin-depleted Xenopus embryos rescued a complete dorsal axis. Xnrs mediate the signal of the Nieuwkoop center that induces the Spemann–Mangold organizer in the overlying mesoderm, a process inhibited by the Nodal antagonist Cerberus-short (CerS). However, β-catenin also induces a second signaling center in the dorsal prospective ectoderm, designated the Blastula Chordin and Noggin Expression (BCNE) center, in which the homeobox gene siamois ( sia ) plays a major role. In this study, we asked whether the Xnrs and Sia depend on each other or function on parallel pathways. Expression of both genes induced β-catenin-depleted embryos to form complete axes with heads and eyes via the activation of similar sets of downstream organizer-specific genes. Xnrs did not activate siamois , and, conversely, Sia did not activate xnrs , although both were induced by β-catenin stabilization. Depletion with morpholinos revealed a robust role for the downstream target Chordin. Remarkably, Chordin depletion prevented all ectopic effects resulting from microinjection of the mRNA encoding the maternal cytoplasmic determinant Huluwa , including the radial expansion of brain tissue and the ectopic expression of the ventral gene sizzled . The main conclusion was that the BCNE and Nieuwkoop centers provide a double assurance mechanism for axial formation by independently activating similar downstream transcriptional target gene repertoires. We suggest that Siamois likely evolved from an ancestral Mix-type homeodomain protein called Sebox as a Xenopus -specific adaptation for the rapid differentiation of the anterior neural plate in the ectoderm.","journal":"Proceedings of the National Academy of Sciences","year":2025,"id":540315,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9519,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":299028,"name":"Edward M. De Robertis","orcid":"0000-0002-7843-1869","position":1,"is_corresponding":false},{"id":1080558,"name":"Yagmur Azbazdar","orcid":"0000-0003-0806-1003","position":0,"is_corresponding":true}],"reference_count":83,"raw_metadata":null,"created_at":"2026-07-19T02:52:38.861025Z","pmid":"39928870","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":[]}