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We describe here a novel mechanism that promotes sexually dimorphic neuronal function and synaptic connectivity in the nervous system of the nematode\n                    <jats:italic>Caenorhabditis elegans<\/jats:italic>\n                    . We demonstrate that a phylogenetically conserved, but previously uncharacterized Doublesex\/Mab-3 related transcription factor (DMRT),\n                    <jats:italic>dmd-4<\/jats:italic>\n                    , is expressed in two classes of sex-shared phasmid neurons specifically in hermaphrodites but not in males. We find\n                    <jats:italic>dmd-4<\/jats:italic>\n                    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.\n                  <\/jats:p>","DOI":"10.7554\/elife.59614","type":"journal-article","created":{"date-parts":[[2020,9,30]],"date-time":"2020-09-30T20:00:32Z","timestamp":1601496032000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.59614","source":"Crossref","is-referenced-by-count":39,"title":["Ubiquitin-dependent regulation of a conserved DMRT protein controls sexually dimorphic synaptic connectivity and behavior"],"prefix":"10.7554","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5254-9199","authenticated-orcid":true,"given":"Emily A","family":"Bayer","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, Howard Hughes Medical Institute, Columbia University, New York, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca 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