{"doi":"10.7554/elife.59614","title":"Ubiquitin-dependent regulation of a conserved DMRT protein controls sexually dimorphic synaptic connectivity and behavior","abstract":"Sex-specific synaptic connectivity is beginning to emerge as a remarkable, but little explored feature of animal brains. We describe here a novel mechanism that promotes sexually dimorphic neuronal function and synaptic connectivity in the nervous system of the nematode Caenorhabditis elegans . We demonstrate that a phylogenetically conserved, but previously uncharacterized Doublesex/Mab-3 related transcription factor (DMRT), dmd-4 , is expressed in two classes of sex-shared phasmid neurons specifically in hermaphrodites but not in males. We find dmd-4 to promote hermaphrodite-specific synaptic connectivity and neuronal function of phasmid sensory neurons. Sex-specificity of DMD-4 function is conferred by a novel mode of posttranslational regulation that involves sex-specific protein stabilization through ubiquitin binding to a phylogenetically conserved but previously unstudied protein domain, the DMA domain. A human DMRT homolog of DMD-4 is controlled in a similar manner, indicating that our findings may have implications for the control of sexual differentiation in other animals as well.","journal":"eLife","year":2020,"id":63732,"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":42,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9526,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":338413,"name":"Rebecca C. Stecky","orcid":null,"position":1,"is_corresponding":false},{"id":338414,"name":"Lauren Neal","orcid":null,"position":2,"is_corresponding":false},{"id":229150,"name":"Phinikoula S. Katsamba","orcid":"0000-0003-3981-1604","position":3,"is_corresponding":false},{"id":293851,"name":"Göran Ahlsén","orcid":null,"position":4,"is_corresponding":false},{"id":146519,"name":"Vishnu Balaji","orcid":null,"position":5,"is_corresponding":false},{"id":337138,"name":"Thorsten Hoppe","orcid":"0000-0002-4734-9352","position":6,"is_corresponding":false},{"id":105638,"name":"Lawrence Shapiro","orcid":"0000-0001-9943-8819","position":7,"is_corresponding":false},{"id":337139,"name":"Meital Oren‐Suissa","orcid":"0000-0001-9937-8326","position":8,"is_corresponding":false},{"id":233159,"name":"Oliver Hobert","orcid":"0000-0002-7634-2854","position":9,"is_corresponding":false},{"id":337137,"name":"Emily A. Bayer","orcid":"0000-0002-5254-9199","position":0,"is_corresponding":true}],"reference_count":77,"raw_metadata":null,"created_at":"2026-07-18T21:11:24.000992Z","pmid":"33021200","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":[]}