PUBLICATION

Loss of growth differentiation factor 9 causes an arrest of early folliculogenesis in zebrafish-A novel insight into its action mechanism

Authors
Chen, W., Zhai, Y., Zhu, B., Wu, K., Fan, Y., Zhou, X., Liu, L., Ge, W.
ID
ZDB-PUB-221216-26
Date
2022
Source
PLoS Genetics   18: e1010318e1010318 (Journal)
Registered Authors
Chen, Weiting, Fan, Yuqin, Ge, Wei, Zhu, Bo
Keywords
none
MeSH Terms
  • Activins/genetics
  • Activins/metabolism
  • Animals
  • Female
  • Growth Differentiation Factor 9*/genetics
  • Growth Differentiation Factor 9*/metabolism
  • Inhibins/genetics
  • Inhibins/metabolism
  • Male
  • Mice
  • Ovarian Follicle/metabolism
  • Zebrafish*/genetics
  • Zebrafish*/metabolism
(all 13)
PubMed
36520929 Full text @ PLoS Genet.
Abstract
Growth differentiation factor 9 (GDF9) was the first oocyte-specific growth factor identified; however, most information about GDF9 functions comes from studies in the mouse model. In this study, we created a mutant for Gdf9 gene (gdf9-/-) in zebrafish using TALEN approach. The loss of Gdf9 caused a complete arrest of follicle development at primary growth (PG) stage. These follicles eventually degenerated, and all mutant females gradually changed to males through sex reversal, which could be prevented by mutation of the male-promoting gene dmrt1. Interestingly, the phenotypes of gdf9-/- could be rescued by simultaneous mutation of inhibin α (inha-/-) but not estradiol treatment, suggesting a potential role for the activin-inhibin system or its signaling pathway in Gdf9 actions. In gdf9 null follicles, the expression of activin βAa (inhbaa), but not βAb (inhbab) and βB (inhbb), decreased dramatically; however, its expression rebounded in the double mutant (gdf9-/-;inha-/-). These results indicate clearly that the activation of PG follicles to enter the secondary growth (SG) requires intrinsic factors from the oocyte, such as Gdf9, which in turn works on the neighboring follicle cells to trigger follicle activation, probably involving activins. In addition, our data also support the view that estrogens are not involved in follicle activation as recently reported.
Genes / Markers
Marker Marker Type Name
cyp19a1aGENEcytochrome P450, family 19, subfamily A, polypeptide 1a
dmrt1GENEdoublesex and mab-3 related transcription factor 1
eef1a1l1GENEeukaryotic translation elongation factor 1 alpha 1, like 1
egfraGENEepidermal growth factor receptor a (erythroblastic leukemia viral (v-erb-b) oncogene homolog, avian)
fshrGENEfollicle stimulating hormone receptor
gdf9GENEgrowth differentiation factor 9
inhaGENEinhibin subunit alpha
inhbaaGENEinhibin subunit beta Aa
inhbabGENEinhibin subunit beta Ab
inhbbGENEinhibin subunit beta B
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Figures
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Expression
No data available
Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
umo5
    		Small Deletion
    umo15
      		Small Deletion
      umo18
        		Indel
        umo19
          		Indel
          1 - 4 of 4
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          Human Disease / Model
          No data available
          Sequence Targeting Reagents
          Target Reagent Reagent Type
          gdf9TALEN2-gdf9TALEN
          1 - 1 of 1
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          Fish
          No data available
          Antibodies
          No data available
          Orthology
          No data available
          Engineered Foreign Genes
          No data available
          Mapping
          No data available
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          Citation
          Chen, W., Zhai, Y., Zhu, B., Wu, K., Fan, Y., Zhou, X., Liu, L., Ge, W. (2022) Loss of growth differentiation factor 9 causes an arrest of early folliculogenesis in zebrafish-A novel insight into its action mechanism. PLoS Genetics. 18:e1010318e1010318.