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Early gonadal development: exploring Wt1 and Sox9 function.

Jian-Kan Guo¹, Annette Hammes, Marie-Christine Chaboissier

¹Human Molecular Genetics Unit, University of Newcastle upon Tyne, UK.

Novartis Foundation Symposium

|May 7, 2002

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The Wilms tumour suppressor WT1 regulates the sex-determining gene Sry. Ectopic expression of SOX9 in XX gonads induces testis formation, suggesting SOX9 is sufficient for male sex determination in mice.

Area of Science:

Developmental Biology
Genetics
Molecular Biology

Background:

Gonadal development begins with a bipotential primordium capable of differentiating into testes or ovaries.
Sex determination is primarily regulated by the Sry gene.
Five genes (Wt1, Sf1, Lim1, Lhx9, Emx2) are implicated in gonadal primordium formation or survival.

Purpose of the Study:

To investigate the role of Wilms tumour suppressor WT1 in sex determination.
To analyze the function of Sox9 in mouse gonad development and sex determination.

Main Methods:

In vitro and in vivo experiments to study WT1 function.
Transgenic experiments involving ectopic expression of Sox9 in XX gonads.

Main Results:

Related Experiment Videos

WT1 regulates the transcription or stability of the Sry gene.
Sox9 is sufficient to induce testis formation in XX gonads, indicating its role in male sex determination.

Conclusions:

WT1 plays a crucial role in regulating Sry, a key gene in male sex determination.
Sox9 is a potent inducer of testis formation and is sufficient for male sex determination in mice.
An updated model for the function of Wt1 and Sox9 in gonad formation and sex determination is presented.