Ovol1 regulates meiotic pachytene progression during spermatogenesis by repressing Id2 expression

Development. 2005 Mar;132(6):1463-73. doi: 10.1242/dev.01658. Epub 2005 Feb 16.

Abstract

Previous studies have shown that a targeted deletion of Ovol1 (previously known as movo1), encoding a member of the Ovo family of zinc-finger transcription factors, leads to germ cell degeneration and defective sperm production in adult mice. To explore the cellular and molecular mechanism of Ovol1 function, we have examined the mutant testis phenotype during the first wave of spermatogenesis in juvenile mice. Consistent with the detection of Ovol1 transcripts in pachytene spermatocytes of the meiotic prophase, Ovol1-deficient germ cells were defective in progressing through the pachytene stage. The pachytene arrest was accompanied by an inefficient exit from proliferation, increased apoptosis and an abnormal nuclear localization of the G2-M cell cycle regulator cyclin B1, but was not associated with apparent chromosomal or recombination defects. Transcriptional profiling and northern blot analysis revealed reduced expression of pachytene markers in the mutant, providing molecular evidence that pachytene differentiation was defective. In addition, the expression of Id2 (inhibitor of differentiation 2), a known regulator of spermatogenesis, was upregulated in Ovol1-deficient pachytene spermatocytes and repressed by Ovol1 in reporter assays. Taken together, our studies demonstrate a role for Ovol1 in regulating pachytene progression of male germ cells, and identify Id2 as a Ovol1 target.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Biomarkers
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Gene Expression Profiling
  • Genes, Reporter
  • Inhibitor of Differentiation Protein 2
  • Male
  • Mice
  • Mutation
  • Pachytene Stage / genetics
  • Pachytene Stage / physiology*
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Spermatogenesis / genetics
  • Spermatogenesis / physiology*
  • Testis / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • Biomarkers
  • DNA-Binding Proteins
  • Idb2 protein, mouse
  • Inhibitor of Differentiation Protein 2
  • Ovo1 protein, mouse
  • Repressor Proteins
  • Transcription Factors