Antagonism of the testis- and ovary-determining pathways during ovotestis development in mice

Mech Dev. May-Jun 2009;126(5-6):324-36. doi: 10.1016/j.mod.2009.02.006. Epub 2009 Mar 6.

Abstract

Ovotestis development in B6-XY(POS) mice provides a rare opportunity to study the interaction of the testis- and ovary-determining pathways in the same tissue. We studied expression of several markers of mouse fetal testis (SRY, SOX9) or ovary (FOXL2, Rspo1) development in B6-XY(POS) ovotestes by immunofluorescence, using normal testes and ovaries as controls. In ovotestes, SOX9 was expressed only in the central region where SRY is expressed earliest, resulting in testis cord formation. Surprisingly, FOXL2-expressing cells also were found in this region, but individual cells expressed either FOXL2 or SOX9, not both. At the poles, even though SOX9 was not up-regulated, SRY expression was down-regulated normally as in XY testes, and FOXL2 was expressed from an early stage, demonstrating ovarian differentiation in these areas. Our data (1) show that SRY must act within a specific developmental window to activate Sox9; (2) challenge the established view that SOX9 is responsible for down-regulating Sry expression; (3) disprove the concept that testicular and ovarian cells occupy discrete domains in ovotestes; and (4) suggest that FOXL2 is actively suppressed in Sertoli cell precursors by the action of SOX9. Together these findings provide important new insights into the molecular regulation of testis and ovary development.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • DNA-Binding Proteins / metabolism
  • Down-Regulation / genetics
  • Female
  • Forkhead Box Protein L2
  • Forkhead Transcription Factors / metabolism
  • Gene Expression Regulation, Developmental
  • Male
  • Mice
  • Ovary / cytology
  • Ovary / embryology*
  • Ovary / metabolism
  • RNA Splicing Factors
  • SOX9 Transcription Factor / metabolism
  • Sex Determination Processes*
  • Sex-Determining Region Y Protein / genetics
  • Sex-Determining Region Y Protein / metabolism
  • Testis / cytology
  • Testis / embryology*
  • Testis / metabolism
  • Time Factors
  • Transcription Factors / metabolism

Substances

  • Biomarkers
  • DNA-Binding Proteins
  • Forkhead Box Protein L2
  • Forkhead Transcription Factors
  • Foxl2 protein, mouse
  • RNA Splicing Factors
  • SOX9 Transcription Factor
  • Sex-Determining Region Y Protein
  • Sf1 protein, mouse
  • Sox9 protein, mouse
  • Transcription Factors