title: Sequential, Divergent, and Cooperative Requirements ofFoxl2aandFoxl2bin Ovary Development and Maintenance of Zebrafish.
abstract: Foxl2is essential for mammalian ovary maintenance. Although sexually dimorphic expression offoxl2was observed in many teleosts, its role and regulative mechanism in fish remained largely unclear. In this study, we first identified two transcript variants offoxl2aand its homologous genefoxl2bin zebrafish, and revealed their specific expression in follicular layer cells in a sequential and divergent fashion during ovary differentiation, maturation, and maintenance. Then, homozygousfoxl2amutants (foxl2a-/-) andfoxl2bmutants (foxl2b-/-) were constructed and detailed comparisons, such as sex ratio, gonadal histological structure, transcriptome profiling, and dynamic expression of gonadal development-related genes, were carried out. Initial ovarian differentiation and oocyte development occur normally both infoxl2a-/-andfoxl2b-/-mutants, butfoxl2aandfoxl2bdisruptions result in premature ovarian failure and partial sex reversal, respectively, in adult females. Infoxl2a-/-female mutants,sox9a-amh/cyp19a1asignaling was upregulated at 150 days postfertilization (dpf) and subsequently oocyte apoptosis was triggered after 180 dpf. In contrast,dmrt1expression was greater at 105 dpf and increased several 100-fold infoxl2b-/-mutated ovaries at 270 dpf, along with other testis-related genes. Finally, homozygousfoxl2a-/-/foxl2b-/-double mutants were constructed in which complete sex reversal occurs early and testis-differentiation genes robustly increase at 60 dpf. Given mutual compensation betweenfoxl2aandfoxl2binfoxl2b-/-andfoxl2a-/-mutants, we proposed a model in whichfoxl2aandfoxl2bcooperate to regulate zebrafish ovary development and maintenance, withfoxl2bpotentially having a dominant role in preventing the ovary from differentiating as testis, as compared tofoxl2a.
authors.affiliation: State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China.|Graduate University of the Chinese Academy of Sciences, Wuhan 430072, China.
authors.forename: Yan-Jing
authors.initials: YJ
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Li
authors.affiliation: State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China jfgui@ihb.ac.cn zhouli@ihb.ac.cn.
authors.forename: Li
authors.initials: L
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China jfgui@ihb.ac.cn zhouli@ihb.ac.cn.
authors.forename: Jian-Fang
authors.initials: JF
authors.lastname: Gui
mesh_terms: D000818:Animals; D001141:Aromatase / Q000235:genetics / Q000378:metabolism; D005260:Female; D000074842:Forkhead Box Protein L2; D051858:Forkhead Transcription Factors / Q000235:genetics* / Q000378:metabolism; D006720:Homozygote; D008297:Male; D009154:Mutation; D009866:Oogenesis; D010053:Ovary / Q000254:growth & development / Q000378:metabolism*; D055758:SOX9 Transcription Factor / Q000235:genetics / Q000378:metabolism; D019849:Sex Determination Processes; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015027:Zebrafish / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D029961:Zebrafish Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: C110547:DMRT1 protein; D000074842:Forkhead Box Protein L2; D051858:Forkhead Transcription Factors; D055758:SOX9 Transcription Factor; C504918:Sox9a protein, zebrafish; D014157:Transcription Factors; D029961:Zebrafish Proteins; C580817:foxl2a protein, zebrafish; D001141:Aromatase; C440729:Cyp19a1a protein, zebrafish
keywords: Foxl2a; Foxl2b; TALEN; premature ovarian failure; sex reversal