nr0b1 (DAX1) mutation in zebrafish causes female-to-male sex reversal through abnormal gonadal proliferation and differentiation.
Sex determinations are diverse in vertebrates. Although many sex-determining genes and pathways are conserved, the mechanistic roles of these genes and pathways in the genetic sex determination are not well understood. DAX1 (encoded by the NR0B1 gene) is a vertebrate specific orphan nuclear receptor that regulates gonadal development and sexual determination. In human, duplication of the NR0B1 gene leads to male-to-female sex reversal. In mice, Nr0b1 shows both pro-testis and anti-testis functions. We generated inheritable nr0b1 mutation in the zebrafish and found the nr0b1 mutation caused homozygous mutants to develop as fertile males due to female-to-male sex reversal. The nr0b1 mutation did not increase Caspase-3 labeling nor tp53 expression in the developing gonads. Introduction of a tp53 mutation into the nr0b1 mutant did not rescue the sex-reversal phenotype. Further examination revealed reduction in cell proliferation and abnormal somatic cell differentiation in the nr0b1 mutant gonads at the undifferentiated and bi-potential ovary stages. Together, our results suggest nr0b1 regulates somatic cell differentiation and cell proliferation to ensure normal sex development in the zebrafish.
Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, 200032, China.
Sijie
S
Chen
Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, 200032, China.
Hefei
H
Zhang
Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, 200032, China.
Fenghua
F
Wang
Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, 200032, China.
Wei
W
Zhang
Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, 200032, China. Electronic address: gangpeng@fudan.edu.cn.
Gang
G
Peng
D000818:Animals; D053148:Caspase 3 / Q000235:genetics; D002454:Cell Differentiation / Q000502:physiology*; D049109:Cell Proliferation / Q000502:physiology*; D057137:DAX-1 Orphan Nuclear Receptor / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D012734:Disorders of Sex Development / Q000235:genetics / Q000473:pathology; D005260:Female; D006066:Gonads / Q000502:physiology*; D008297:Male; D009154:Mutation / Q000235:genetics*; D010053:Ovary / Q000502:physiology; D019849:Sex Determination Processes / Q000235:genetics; D012733:Sex Differentiation / Q000235:genetics; D013737:Testis / Q000502:physiology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D015027:Zebrafish / Q000235:genetics* / Q000502:physiology*
D057137:DAX-1 Orphan Nuclear Receptor; D004268:DNA-Binding Proteins; D016159:Tumor Suppressor Protein p53; D053148:Caspase 3
DAX1; Sex determination; Somatic cell; Zebrafish; nr0b1