PUBLICATION

Disruption of dmrt1 rescues the all-male phenotype of cyp19a1a mutant in zebrafish - A Novel insight into the roles of aromatase/estrogens in gonadal differentiation and early folliculogenesis

Authors
Wu, K., Song, W., Zhang, Z., Ge, W.
ID
ZDB-PUB-200201-4
Date
2020
Source
Development (Cambridge, England)   147(4): (Journal)
Registered Authors
Ge, Wei, Zhang, Zhiwei
Keywords
Aromatase, Cyp19a1a, Dmrt1, Folliculogenesis, Sex differentiation, Zebrafish
MeSH Terms
  • Alleles
  • Animals
  • Animals, Genetically Modified
  • Aromatase/genetics*
  • Aromatase/physiology*
  • Cell Differentiation
  • Estrogens/physiology
  • Female
  • Gene Knockout Techniques
  • Genotype
  • Heterozygote
  • Male
  • Mutation
  • Ovarian Follicle/embryology*
  • Phenotype
  • Receptors, Estrogen/physiology
  • Sex Determination Processes
  • Sex Differentiation
  • Testis/embryology*
  • Transcription Factors/genetics*
  • Zebrafish
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/physiology*
PubMed
32001440 Full text @ Development
Abstract
Sex determination and differentiation are complex processes controlled by many different factors; however, the relationships among these factors are poorly understood. Zebrafish gonadal differentiation exhibits high plasticity involving multiple factors and pathways, which provides an excellent model for investigating the interactions among them. Ovarian aromatase (cyp19a1a) and dmrt1 are key factors in directing vertebrate ovary and testis differentiation, respectively. Knockout of zebrafish cyp19a1a led to all-male offspring, whereas the loss of dmrt1 resulted in a female-biased sex ratio. In the present study, we established dmrt1-/-;cyp19a1a-/- double mutant zebrafish and discovered that the introduction of the dmrt1 mutation into the cyp19a1a mutant could rescue the all-male phenotype of the latter. Interestingly, despite the lack of aromatase/estrogens, the follicles in the ovary of the rescued cyp19a1a mutant could develop normally up to the previtellogenic stage (PV). Further evidence suggested the ovarian aromatase directed ovarian differentiation by suppressing dmrt1 expression via nuclear estrogen receptors (nERs). Our results provide solid evidence for an interaction between cyp19a1a and dmrt1 in zebrafish gonadal differentiation and for the dispensability of estrogens in controlling early folliculogenesis.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping