{"doi":"10.1101/2022.05.05.490791","title":"Maintenance of neurotransmitter identity by Hox proteins through a homeostatic mechanism","abstract":"SUMMARY Hox transcription factors play fundamental roles during early patterning, but they are also expressed continuously – from embryo through adulthood – in the nervous system. The functional significance of their sustained expression remains unclear. In C. elegans motor neurons (MNs), we find that LIN-39 (Scr/Dfd/Hox4-5) is continuously required during post-embryonic life to maintain neurotransmitter identity, a core element of neuronal function. LIN-39 acts directly to co-regulate genes that define cholinergic identity (e.g., unc-17/VAChT, cho-1/ChT ). We further show that LIN-39, MAB-5 (Antp/Hox6-8) and the transcription factor UNC-3 (Collier/Ebf) operate in a positive feedforward loop to ensure continuous and robust expression of cholinergic identity genes. Finally, we identify a two-component, design principle (Hox transcriptional autoregulation counterbalanced by negative UNC-3 feedback) for homeostatic control of Hox gene expression in adult MNs. These findings uncover a noncanonical role for Hox proteins during post-embryonic life, critically broadening their functional repertoire from early patterning to the control of neurotransmitter identity.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":303246,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9523,"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":894372,"name":"Honorine Destain","orcid":"0000-0002-6581-6372","position":1,"is_corresponding":false},{"id":308273,"name":"Jayson J. Smith","orcid":"0000-0001-8525-7873","position":2,"is_corresponding":false},{"id":323687,"name":"Paschalis Kratsios","orcid":"0000-0002-1363-9271","position":3,"is_corresponding":false},{"id":324791,"name":"Weidong Feng","orcid":null,"position":0,"is_corresponding":true}],"reference_count":67,"raw_metadata":null,"created_at":"2026-07-19T00:32:24.307938Z","pmid":null,"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":[]}