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In the fish medaka, the Y-chromosomal <jats:italic>dmy<\/jats:italic> (also <jats:italic>dmrt1bY<\/jats:italic>) serves the sex determiner, which activates <jats:italic>dmrt1<\/jats:italic> for male sex maintenance. However, how <jats:italic>dmy<\/jats:italic> makes the male decision via initiating testicular differentiation has remained unknown. Here we report that autosomal <jats:italic>gsdf<\/jats:italic> serves a male sex initiator. Gene addition and deletion revealed that <jats:italic>gsdf<\/jats:italic> was necessary and sufficient for maleness via initiating testicular differentiation. We show that <jats:italic>gsdf<\/jats:italic> transcription is activated directly by <jats:italic>dmy<\/jats:italic>. These results establish the autosomal <jats:italic>gsdf<\/jats:italic> as the first male sex initiator. We propose that <jats:italic>dmy<\/jats:italic> determines maleness through activating <jats:italic>gsdf<\/jats:italic> and <jats:italic>dmrt1<\/jats:italic> without its own participation in developmental processes of sex initiation and maintenance. <jats:italic>gsdf<\/jats:italic> may easily become a sex determiner or other autosomal genes can be recruited as new sex determiners to initiate <jats:italic>gsdf<\/jats:italic> expression. Our findings offer new insights into molecular mechanisms underlying sex development and evolution of sex-controlling genes in vertebrates.<\/jats:p>","DOI":"10.1038\/srep19738","type":"journal-article","created":{"date-parts":[[2016,1,27]],"date-time":"2016-01-27T10:27:05Z","timestamp":1453890425000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":109,"title":["Autosomal gsdf acts as a male sex initiator in the fish medaka"],"prefix":"10.1038","volume":"6","author":[{"given":"Xi","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guijun","family":"Guan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingyou","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qizhi","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiyoshi","family":"Naruse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amaury","family":"Herpin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshitaka","family":"Nagahama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiale","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunhan","family":"Hong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,1,27]]},"reference":[{"key":"BFsrep19738_CR1","doi-asserted-by":"publisher","first-page":"1268","DOI":"10.1126\/science.aaa2850","volume":"348","author":"AB Hall","year":"2015","unstructured":"Hall, A. 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