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and sex-specific prevalence. ARHGEF10 encodes a conserved guanine exchange factor that activates Rho GTPases and has proposed roles in cell migration and adhesion, but the relevant cell types and mechanisms underlying its age- and sex-dependent effects remain unclear. Drosophila darhgef10 gene is the single orthologue of vertebrate ARHGEF10 and its paralogue ARHGEF10L. Here, to gain insight into possible age- and sex-dependent ARHGEF10 neuromuscular functions, we generated darhgef10 knockout flies and quantified induced walking kinematics with high-speed imaging and coarse spontaneous behaviors\u2014walking, micromovements, and sleep\u2014in open arenas. Mutants of both sexes exhibited abnormal walking kinematics, which worsened with age in females. Cell-type-specific knockdowns indicated these phenotypes arose primarily from neuronal, rather than glial or muscle, requirements. Loss of darhgef10 also caused sexually dimorphic neurodevelopmental and post-adult-onset behavioral effects: females were more susceptible to total darhgef10 reduction, showing decreased wakefulness and speed. In contrast, darhgef10 isoform imbalance\u2014rather than total loss\u2014drove stronger locomotor effects in males, suggesting complex activity regulation. These sexually dimorphic effects were also largely explained by neuronal darhgef10 activity. Accordingly, dArhgef10 expression was detected in the developing nervous system, where motor neuron-targeted knockdown demonstrated a cell-autonomous requirement in establishing adult muscle innervation patterns. ARHGEF10 thus plays an ancient, conserved role in neurons that promotes proper wakefulness and locomotor activity in an age- and sex-dependent manner.<\/jats:p>","DOI":"10.1093\/genetics\/iyag237","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T08:20:15Z","timestamp":1788423615000},"source":"Crossref","is-referenced-by-count":0,"title":["Sex-specific control of locomotor behavior by neuronal Arhgef10 in aged\n                    <i>Drosophila<\/i>"],"prefix":"10.1093","author":[{"given":"Mafalda","family":"Gualdino","sequence":"first","affiliation":[{"name":"cE3c - Centre for Ecology, Evolution and Environmental Changes & CHANGE - Global Change and Sustainability Institute, Departamento de Biologia, Faculdade de Ci\u00eancias, Universidade de Lisboa, 1749-016 Lisboa ,","place":["Portugal"]},{"name":"iNOVA4Health, Nova Medical School, Faculdade de Ci\u00eancias M\u00e9dicas, NMS, FCM, Universidade Nova de Lisboa , 1150-082 Lisboa ,","place":["Portugal"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabiana","family":"Her\u00e9dia","sequence":"additional","affiliation":[{"name":"cE3c - Centre for Ecology, Evolution and Environmental Changes & CHANGE - Global Change and Sustainability Institute, Departamento de Biologia, Faculdade de Ci\u00eancias, Universidade de Lisboa, 1749-016 Lisboa ,","place":["Portugal"]},{"name":"iNOVA4Health, Nova Medical School, Faculdade de Ci\u00eancias M\u00e9dicas, NMS, FCM, Universidade Nova de Lisboa , 1150-082 Lisboa ,","place":["Portugal"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra M","family":"Medeiros","sequence":"additional","affiliation":[{"name":"iNOVA4Health, Nova Medical School, Faculdade de Ci\u00eancias M\u00e9dicas, NMS, FCM, Universidade Nova de Lisboa , 1150-082 Lisboa ,","place":["Portugal"]},{"name":"Biozentrum, Universit\u00e4t Basel , Spitalstrasse 41, Basel 4056 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,","place":["Portugal"]},{"name":"iNOVA4Health, Nova Medical School, Faculdade de Ci\u00eancias M\u00e9dicas, NMS, FCM, Universidade Nova de Lisboa , 1150-082 Lisboa ,","place":["Portugal"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,9,3]]},"reference":[{"key":"2026091621564753700_iyag237-B1","doi-asserted-by":"publisher","first-page":"417","DOI":"10.3109\/09540261.2010.515205","article-title":"Sex differences in schizophrenia","volume":"22","author":"Abel","year":"2010","journal-title":"Int Rev Psychiatry"},{"key":"2026091621564753700_iyag237-B2","volume-title":"Anaconda (version 2022.05\/python 3.9.13) [computer software]","author":"Anaconda Software Distribution","year":"2022"},{"key":"2026091621564753700_iyag237-B3","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1101\/lm.5.1.102","article-title":"Metamorphosis of the mushroom bodies; large-scale rearrangements of the neural substrates for associative 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