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Sex-determining genes in mice: building pathways.
Robin Lovell-Badge1, Clare Canning, Ryohei Sekido
1Division of Developmental Genetics, MRC National Institute for Medical Research, London, UK.
Novartis Foundation Symposium
|May 7, 2002
Summary
The SRY gene initiates Sertoli cell differentiation in mice by directly upregulating SOX9. Steroidogenic factor 1 (SF1) also plays a key role in gonadal development by activating genes like SOX9 and AMH.
Area of Science:
- Genetics
- Developmental Biology
- Molecular Biology
Background:
- Sry gene initiates Sertoli cell differentiation in mouse genital ridge.
- Sertoli cell differentiation requires SRY and other gene products.
- Several genes (e.g., Lhx9, Wt1, Sf1, Dax1, Gata4, Dmrt1, Sox9, Amh, Wnt4, Dhh) are crucial for gonadal development and sex determination.
Purpose of the Study:
- To elucidate the regulatory network of genes involved in mammalian sex determination and gonadal development.
- To investigate the direct interaction between SRY and SOX9.
- To understand the role of SF1 in activating genes essential for gonadal differentiation.
Main Methods:
- Analysis of gene regulatory networks in mouse gonadal development.
- Experimental data suggesting direct SRY regulation of SOX9.
- Investigation of SF1's transcriptional activation capabilities.
Main Results:
- SOX9 is critical for initiating and maintaining Sertoli cell differentiation in mammals.
- Evidence suggests SRY directly upregulates SOX9.
- SF1 activates multiple genes, including SOX9 and AMH, and also genes with antagonistic effects like DAX1.
Conclusions:
- SRY likely initiates Sertoli cell differentiation by directly activating SOX9.
- SF1 is a central regulator in gonadal differentiation, influencing both male-specific and other developmental pathways.
- Further research is ongoing to establish additional regulatory interactions in gonadal development.