Genetic evidence for differential functions of figla and nobox in zebrafish ovarian differentiation and folliculogenesis

Abstract FIGLA and NOBOX are important oocyte-specific transcription factors. Both figla-/- and nobox-/- mutants showed all-male phenotype in zebrafish due to increased dominance of the male-promoting pathway. The early diversion towards males in these mutants has precluded analysis of their roles i...

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Main Authors: Kun Wu, Yue Zhai, Mingming Qin, Cheng Zhao, Nana Ai, Jianguo He, Wei Ge
Format: Article
Language:English
Published: Nature Portfolio 2023-11-01
Series:Communications Biology
Online Access:https://doi.org/10.1038/s42003-023-05551-1
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author Kun Wu
Yue Zhai
Mingming Qin
Cheng Zhao
Nana Ai
Jianguo He
Wei Ge
author_facet Kun Wu
Yue Zhai
Mingming Qin
Cheng Zhao
Nana Ai
Jianguo He
Wei Ge
author_sort Kun Wu
collection DOAJ
description Abstract FIGLA and NOBOX are important oocyte-specific transcription factors. Both figla-/- and nobox-/- mutants showed all-male phenotype in zebrafish due to increased dominance of the male-promoting pathway. The early diversion towards males in these mutants has precluded analysis of their roles in folliculogenesis. In this study, we attenuated the male-promoting pathway by deleting dmrt1, a key male-promoting gene, in figla-/- and nobox-/- fish, which allows a sufficient display of defects in folliculogenesis. Germ cells in figla-/-;dmrt1-/- double mutant remained in cysts without forming follicles. In contrast, follicles could form well but exhibited deficient growth in nobox-/-;dmrt1-/- double mutants. Follicles in nobox-/-;dmrt1-/- ovary could progress to previtellogenic (PV) stage but failed to enter vitellogenic growth. Such arrest at PV stage suggested a possible deficiency in estrogen signaling. This was supported by lines of evidence in nobox-/-;dmrt1-/-, including reduced expression of ovarian aromatase (cyp19a1a) and level of serum estradiol (E2), regressed genital papilla (female secondary sex characteristics), and more importantly the resumption of vitellogenic growth by E2 treatment. Expression analysis suggested Nobox might regulate cyp19a1a by controlling Gdf9 and/or Bmp15. Our discoveries indicate that Figla is essential for ovarian differentiation and follicle formation whereas Nobox is important for driving subsequent follicle development.
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spelling doaj.art-01f1dc8033f044a49153f75368befe0c2023-12-17T12:27:12ZengNature PortfolioCommunications Biology2399-36422023-11-016111410.1038/s42003-023-05551-1Genetic evidence for differential functions of figla and nobox in zebrafish ovarian differentiation and folliculogenesisKun Wu0Yue Zhai1Mingming Qin2Cheng Zhao3Nana Ai4Jianguo He5Wei Ge6Department of Biomedical Sciences and Centre of Reproduction, Development and Aging (CRDA), Faculty of Health Sciences, University of MacauDepartment of Biomedical Sciences and Centre of Reproduction, Development and Aging (CRDA), Faculty of Health Sciences, University of MacauDepartment of Biomedical Sciences and Centre of Reproduction, Development and Aging (CRDA), Faculty of Health Sciences, University of MacauDepartment of Biomedical Sciences and Centre of Reproduction, Development and Aging (CRDA), Faculty of Health Sciences, University of MacauDepartment of Biomedical Sciences and Centre of Reproduction, Development and Aging (CRDA), Faculty of Health Sciences, University of MacauSchool of Marine Sciences, Sun Yat-sen UniversityDepartment of Biomedical Sciences and Centre of Reproduction, Development and Aging (CRDA), Faculty of Health Sciences, University of MacauAbstract FIGLA and NOBOX are important oocyte-specific transcription factors. Both figla-/- and nobox-/- mutants showed all-male phenotype in zebrafish due to increased dominance of the male-promoting pathway. The early diversion towards males in these mutants has precluded analysis of their roles in folliculogenesis. In this study, we attenuated the male-promoting pathway by deleting dmrt1, a key male-promoting gene, in figla-/- and nobox-/- fish, which allows a sufficient display of defects in folliculogenesis. Germ cells in figla-/-;dmrt1-/- double mutant remained in cysts without forming follicles. In contrast, follicles could form well but exhibited deficient growth in nobox-/-;dmrt1-/- double mutants. Follicles in nobox-/-;dmrt1-/- ovary could progress to previtellogenic (PV) stage but failed to enter vitellogenic growth. Such arrest at PV stage suggested a possible deficiency in estrogen signaling. This was supported by lines of evidence in nobox-/-;dmrt1-/-, including reduced expression of ovarian aromatase (cyp19a1a) and level of serum estradiol (E2), regressed genital papilla (female secondary sex characteristics), and more importantly the resumption of vitellogenic growth by E2 treatment. Expression analysis suggested Nobox might regulate cyp19a1a by controlling Gdf9 and/or Bmp15. Our discoveries indicate that Figla is essential for ovarian differentiation and follicle formation whereas Nobox is important for driving subsequent follicle development.https://doi.org/10.1038/s42003-023-05551-1
spellingShingle Kun Wu
Yue Zhai
Mingming Qin
Cheng Zhao
Nana Ai
Jianguo He
Wei Ge
Genetic evidence for differential functions of figla and nobox in zebrafish ovarian differentiation and folliculogenesis
Communications Biology
title Genetic evidence for differential functions of figla and nobox in zebrafish ovarian differentiation and folliculogenesis
title_full Genetic evidence for differential functions of figla and nobox in zebrafish ovarian differentiation and folliculogenesis
title_fullStr Genetic evidence for differential functions of figla and nobox in zebrafish ovarian differentiation and folliculogenesis
title_full_unstemmed Genetic evidence for differential functions of figla and nobox in zebrafish ovarian differentiation and folliculogenesis
title_short Genetic evidence for differential functions of figla and nobox in zebrafish ovarian differentiation and folliculogenesis
title_sort genetic evidence for differential functions of figla and nobox in zebrafish ovarian differentiation and folliculogenesis
url https://doi.org/10.1038/s42003-023-05551-1
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