{"doi":"10.1093/nar/gkac730","title":"Dichotomous<i>cis</i>-regulatory motifs mediate the maturation of the neuromuscular junction by retrograde BMP signaling","abstract":"Retrograde bone morphogenetic protein (BMP) signaling at the Drosophila neuromuscular junction (NMJ) has served as a paradigm to study TGF-β-dependent synaptic function and maturation. Yet, how retrograde BMP signaling transcriptionally regulates these functions remains unresolved. Here, we uncover a gene network, enriched for neurotransmission-related genes, that is controlled by retrograde BMP signaling in motor neurons through two Smad-binding cis-regulatory motifs, the BMP-activating (BMP-AE) and silencer (BMP-SE) elements. Unpredictably, both motifs mediate direct gene activation, with no involvement of the BMP derepression pathway regulators Schnurri and Brinker. Genome editing of candidate BMP-SE and BMP-AE within the locus of the active zone gene bruchpilot, and a novel Ly6 gene witty, demonstrated the role of these motifs in upregulating genes required for the maturation of pre- and post-synaptic NMJ compartments. Our findings uncover how Smad-dependent transcriptional mechanisms specific to motor neurons directly orchestrate a gene network required for synaptic maturation by retrograde BMP signaling.","journal":"Nucleic Acids Research","year":2022,"id":279669,"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":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9496,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":953732,"name":"Mo Miao","orcid":null,"position":1,"is_corresponding":false},{"id":953733,"name":"Sonia Medina-Giro","orcid":null,"position":2,"is_corresponding":false},{"id":953243,"name":"Clara-Maria Ell","orcid":"0000-0002-8070-3149","position":3,"is_corresponding":false},{"id":367487,"name":"Stéphane Flibotte","orcid":"0000-0001-9613-7666","position":4,"is_corresponding":false},{"id":953244,"name":"Tianshun Lian","orcid":"0000-0001-6359-7244","position":5,"is_corresponding":false},{"id":776527,"name":"Grant Kauwe","orcid":null,"position":6,"is_corresponding":false},{"id":953245,"name":"Annie Collins","orcid":"0000-0002-2974-8181","position":7,"is_corresponding":false},{"id":953246,"name":"Sophia Ly","orcid":"0000-0002-1212-564X","position":8,"is_corresponding":false},{"id":953247,"name":"George Pyrowolakis","orcid":"0000-0002-2142-5943","position":9,"is_corresponding":false},{"id":953248,"name":"A. Pejmun Haghighi","orcid":"0000-0002-4928-3609","position":10,"is_corresponding":false},{"id":758850,"name":"Douglas W. Allan","orcid":"0000-0002-3488-8365","position":11,"is_corresponding":false},{"id":953731,"name":"Robin Vuilleumier","orcid":null,"position":0,"is_corresponding":true}],"reference_count":75,"raw_metadata":null,"created_at":"2026-07-19T00:28:55.546964Z","pmid":"36029115","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":[]}