Zebrafish Foxl2l functions in proliferating germ cells for female meiotic entry

Dev Biol. 2025 Jan:517:91-99. doi: 10.1016/j.ydbio.2024.09.013. Epub 2024 Sep 26.

Abstract

Zebrafish sex differentiation is a complicated process and the detailed mechanism has not been fully understood. Here we characterized a transcription factor, Foxl2l, which participates in female oogenesis. We show that it is expressed specifically in proliferating germ cells in juvenile gonads and mature ovaries. We have used CRISPR-Cas9 to generate zebrafish deficient in foxl2l expression. Zebrafish with foxl2l-/- are all males, and this female-to-male sex reversal cannot be reversed by tp53 mutation, indicating this sex reversal is unrelated to cell death. We have generated transgenic fish expressing GFP under the control of foxl2l promoter to track the development of foxl2l + -germ cells; these cells failed to enter meiosis and accumulated as cystic cells in the foxl2l-/- mutant. Our RNA-seq analysis also showed the reduced expression of genes in meiosis and oogenesis among other affected pathways. All together, we show that zebrafish Foxl2l is a nuclear factor controlling the expression of meiotic and oogenic genes, and its deficiency leads to defective meiotic entry and the accumulation of premeiotic germ cells.

Keywords: Foxl2l; Meiosis; Oogenesis; RNA-Seq; Sex differentiation; Transcriptome.

MeSH terms

  • Animals
  • Animals, Genetically Modified*
  • CRISPR-Cas Systems / genetics
  • Cell Proliferation / genetics
  • Female
  • Forkhead Box Protein L2 / genetics
  • Forkhead Box Protein L2 / metabolism
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / metabolism
  • Gene Expression Regulation, Developmental / genetics
  • Germ Cells* / cytology
  • Germ Cells* / metabolism
  • Male
  • Meiosis* / genetics
  • Oogenesis* / genetics
  • Oogenesis* / physiology
  • Ovary / cytology
  • Ovary / metabolism
  • Sex Differentiation / genetics
  • Zebrafish Proteins* / genetics
  • Zebrafish Proteins* / metabolism
  • Zebrafish* / genetics

Substances

  • Zebrafish Proteins
  • Forkhead Transcription Factors
  • Forkhead Box Protein L2