PUBLICATION

E2f5 is a versatile transcriptional activator required for spermatogenesis and multiciliated cell differentiation in zebrafish

Authors
Xie, H., Kang, Y., Wang, S., Zheng, P., Chen, Z., Roy, S., Zhao, C.
ID
ZDB-PUB-200403-138
Date
2020
Source
PLoS Genetics   16: e1008655 (Journal)
Registered Authors
Roy, Sudipto, Zhao, Chengtian
Keywords
none
MeSH Terms
  • E2F5 Transcription Factor/genetics
  • E2F5 Transcription Factor/metabolism*
  • Signal Transduction
  • Animals
  • Zebrafish
  • Cilia/metabolism
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
  • Spermatogenesis/physiology*
  • Cell Cycle Proteins/physiology
  • Cell Differentiation/physiology
  • Male
  • DNA-Binding Proteins/metabolism
  • Receptors, Notch/metabolism
(all 14)
PubMed
32196499 Full text @ PLoS Genet.
Abstract
E2f5 is a member of the E2f family of transcription factors that play essential roles during many cellular processes. E2f5 was initially characterized as a transcriptional repressor in cell proliferation studies through its interaction with the Retinoblastoma (Rb) protein for inhibition of target gene transcription. However, the precise roles of E2f5 during embryonic and post-embryonic development remain incompletely investigated. Here, we report that zebrafish E2f5 plays critical roles during spermatogenesis and multiciliated cell (MCC) differentiation. Zebrafish e2f5 mutants develop exclusively as infertile males. In the mutants, spermatogenesis is arrested at the zygotene stage due to homologous recombination (HR) defects, which finally leads to germ cell apoptosis. Inhibition of cell apoptosis in e2f5;tp53 double mutants rescued ovarian development, although oocytes generated from the double mutants were still abnormal, characterized by aberrant distribution of nucleoli. Using transcriptome analysis, we identified dmc1, which encodes an essential meiotic recombination protein, as the major target gene of E2f5 during spermatogenesis. E2f5 can bind to the promoter of dmc1 to promote HR, and overexpression of dmc1 significantly increased the fertilization rate of e2f5 mutant males. Besides gametogenesis defects, e2f5 mutants failed to develop MCCs in the nose and pronephric ducts during early embryonic stages, but these cells recovered later due to redundancy with E2f4. Moreover, we demonstrate that ion transporting principal cells in the pronephric ducts, which remain intercalated with the MCCs, do not contain motile cilia in wild-type embryos, while they generate single motile cilia in the absence of E2f5 activity. In line with this, we further show that E2f5 activates the Notch pathway gene jagged2b (jag2b) to inhibit the acquisition of MCC fate as well as motile cilia differentiation by the neighboring principal cells. Taken together, our data suggest that E2f5 can function as a versatile transcriptional activator and identify novel roles of the protein in spermatogenesis as well as MCC differentiation during zebrafish development.
Genes / Markers
Figures
Figure Gallery (6 images)
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
gz32TgTransgenic Insertion
    ouc2017TgTransgenic Insertion
      ouc2018TgTransgenic Insertion
        ouc2019
          Indel
          ouc2020
            Insertion
            ouc2021
              Indel
              ouc2022
                Small Deletion
                ta52b
                  Point Mutation
                  zdf1
                    Point Mutation
                    1 - 9 of 9
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                    Human Disease / Model
                    No data available
                    Sequence Targeting Reagents
                    Target Reagent Reagent Type
                    e2f4CRISPR3-e2f4CRISPR
                    e2f5CRISPR3-e2f5CRISPR
                    1 - 2 of 2
                    Show
                    Fish
                    Antibodies
                    Orthology
                    No data available
                    Engineered Foreign Genes
                    Marker Marker Type Name
                    EGFPEFGEGFP
                    1 - 1 of 1
                    Show
                    Mapping
                    No data available