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Recently, we have shown that compromised androgen and estrogen synthesis with increased progestin leads to all-male differentiation with proper testis development and spermatogenesis in <jats:italic>cytochrome P450 17a1<\/jats:italic> (<jats:italic>cyp17a1<\/jats:italic>)-\/- zebrafish. In the present study, the phenotypes of female-biased sex ratio were positively correlated with higher <jats:italic>Fanconi anemia complementation group L<\/jats:italic> (<jats:italic>fancl<\/jats:italic>) expression in the gonads of <jats:italic>doublesex and mab-3 related transcription factor 1<\/jats:italic> (<jats:italic>dmrt1<\/jats:italic>)-\/- and <jats:italic>cyp17a1<\/jats:italic>-\/-;<jats:italic>dmrt1<\/jats:italic>-\/- fish. The additional depletion of <jats:italic>fancl<\/jats:italic> in <jats:italic>cyp17a1<\/jats:italic>-\/-;<jats:italic>dmrt1<\/jats:italic>-\/- zebrafish reversed the gonadal sex differentiation from all-ovary to all-testis (in <jats:italic>cyp17a1<\/jats:italic>-\/-;<jats:italic>dmrt1<\/jats:italic>-\/-;<jats:italic>fancl<\/jats:italic>-\/- fish). Luciferase assay revealed a synergistic inhibitory effect of Dmrt1 and androgen signaling on <jats:italic>fancl<\/jats:italic> transcription. Furthermore, an interaction between Fancl and the apoptotic factor Tumour protein p53 (Tp53) was found <jats:italic>in vitro<\/jats:italic>. The interaction between Fancl and Tp53 was observed via the WD repeat domain (WDR) and C-terminal domain (CTD) of Fancl and the DNA binding domain (DBD) of Tp53, leading to the K48-linked polyubiquitination degradation of Tp53 activated by the ubiquitin ligase, Fancl. Our results show that testis fate in <jats:italic>cyp17a1<\/jats:italic>-\/- fish is determined by Dmrt1, which is thought to stabilize Tp53 by inhibiting <jats:italic>fancl<\/jats:italic> transcription during the critical stage of sexual fate determination in zebrafish.<\/jats:p>","DOI":"10.1371\/journal.pgen.1011170","type":"journal-article","created":{"date-parts":[[2024,3,7]],"date-time":"2024-03-07T18:24:20Z","timestamp":1709835860000},"page":"e1011170","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgen.corrections_policy","source":"Crossref","is-referenced-by-count":11,"title":["New insights into the all-testis differentiation in zebrafish with compromised endogenous androgen and estrogen synthesis"],"prefix":"10.1371","volume":"20","author":[{"given":"Yonglin","family":"Ruan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuehui","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4124-0102","authenticated-orcid":true,"given":"Gang","family":"Zhai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiyong","family":"Lou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiangyan","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4947-3573","authenticated-orcid":true,"given":"Jie","family":"Mei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wuhan","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianfang","family":"Gui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhan","family":"Yin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,3,7]]},"reference":[{"issue":"8","key":"pgen.1011170.ref001","article-title":"Germline sexual fate is determined by the antagonistic action of dmrt1 and foxl3\/foxl2 in tilapia","volume":"148","author":"S Dai","year":"2021","journal-title":"Development"},{"key":"pgen.1011170.ref002","first-page":"1","volume-title":"The masterpiece of nature: the evolution and genetics of sexuality","author":"G. 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