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delved into the key contribution of gonadal hormones to the generation of sex differences in the developing brain and the expression of sex-specific physiological and behavioral phenotypes in adulthood. However, it was not until recent years that the role of sex chromosomes in the matter started to be seriously explored and unveiled beyond gonadal determination. Now we know that the divergent evolutionary process suffered by X and Y chromosomes has determined that they now encode mostly dissimilar genetic information and are subject to different epigenetic regulations, characteristics that together contribute to generate sex differences between XX and XY cells\/individuals from the zygote throughout life. Here we will review and discuss relevant data showing how particular X- and Y-linked genes and epigenetic mechanisms controlling their expression and inheritance are involved, along with or independently of gonadal hormones, in the generation of sex differences in the brain.<\/jats:p>","DOI":"10.3390\/ijms232012288","type":"journal-article","created":{"date-parts":[[2022,10,17]],"date-time":"2022-10-17T02:29:46Z","timestamp":1665973786000},"page":"12288","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Genetics and Epigenetics of the X and Y Chromosomes in the Sexual Differentiation of the Brain"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3999-9985","authenticated-orcid":false,"given":"Lucas E.","family":"Cabrera Zapata","sequence":"first","affiliation":[{"name":"Instituto de Investigaci\u00f3n M\u00e9dica Mercedes y Mart\u00edn Ferreyra (INIMEC), Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET), Universidad Nacional de C\u00f3rdoba, C\u00f3rdoba 5016, Argentina"},{"name":"Instituto Cajal (IC), Consejo Superior de Investigaciones Cient\u00edficas (CSIC), 28002 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2450-2916","authenticated-orcid":false,"given":"Luis Miguel","family":"Garcia-Segura","sequence":"additional","affiliation":[{"name":"Instituto Cajal (IC), Consejo Superior de Investigaciones Cient\u00edficas (CSIC), 28002 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3738-4699","authenticated-orcid":false,"given":"Mar\u00eda Julia","family":"Cambiasso","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n M\u00e9dica Mercedes y Mart\u00edn Ferreyra (INIMEC), Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET), Universidad Nacional de C\u00f3rdoba, C\u00f3rdoba 5016, Argentina"},{"name":"C\u00e1tedra de Biolog\u00eda Celular, Facultad de Odontolog\u00eda, Universidad Nacional de C\u00f3rdoba, C\u00f3rdoba 5000, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4303-9576","authenticated-orcid":false,"given":"Maria Angeles","family":"Arevalo","sequence":"additional","affiliation":[{"name":"Instituto Cajal (IC), Consejo Superior de Investigaciones Cient\u00edficas (CSIC), 28002 Madrid, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.yfrne.2011.02.007","article-title":"Sexual differentiation of the human brain: Relation to gender identity, sexual orientation and neuropsychiatric disorders","volume":"32","author":"Bao","year":"2011","journal-title":"Front. 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