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Gonadal defects in Cited2-mutant mice indicate a role for SF1 in both testis and ovary differentiation

Alexander N Combes1, Cassy M Spiller, Vincent R Harley

  • 1Division of Molecular Genetics and Development, Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia.

The International Journal of Developmental Biology
|September 17, 2009
PubMed

Insights

The study reveals that the transcription factor SF1 (steroidogenic factor 1) plays a crucial role in both testis and ovary development. Reduced SF1 function in Cited2 mutant mice disrupted testis formation and altered ovarian development, suggesting a novel role in female gonadogenesis.

Area of Science:

  • Developmental Biology
  • Genetics
  • Reproductive Biology

Background:

  • Sex determination involves molecular antagonism between testis and ovary pathways.
  • Genes maintaining the supporting cell lineage are critical for gonadal development.
  • The role of transcription factor SF1 (steroidogenic factor 1) in sex differentiation is not fully understood due to severe loss-of-function phenotypes.

Purpose of the Study:

  • To investigate the sex-specific roles of SF1 in gonadal development using a hypomorphic model.
  • To understand the influence of SF1 on testis and ovary differentiation.

Main Methods:

  • Utilized Cited2(-/-) mice as a hypomorphic model for reduced SF1 expression.
  • Analyzed gonadal development in XY and XX Cited2 mutant mice.
  • Examined gene expression patterns including Fgf9, Wnt4, and Foxl2.

Main Results:

  • XY Cited2(-/-) gonads exhibited delayed testis development and permanently disrupted structure.
  • XX Cited2(-/-) gonads showed ectopic cell migration.
  • Ovarian development in XX Cited2(-/-) gonads was associated with transient Fgf9 upregulation and delayed Wnt4 and Foxl2 expression.

Conclusions:

  • SF1 (steroidogenic factor 1) is essential for normal testis differentiation.
  • SF1 also plays a novel role in promoting ovarian development.
  • Cited2 is important for regulating SF1 function during gonadal development.

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