Key Gene for Ovary Development Identified in Mice

Researchers from the Francis Crick Institute, the Université Cote d’Azur, and other labs in France and Switzerland have identified a critical gene, Wt1, that plays an early role in ovary development in mice, regardless of whether the mice have XX or XY sex chromosomes.

In typical development, mice with XY chromosomes develop testes, while mice with XX chromosomes develop ovaries. Early gonadal development is governed by whether cells become Sertoli cells (for testes) or pregranulosa cells (for ovaries). This is regulated by a set of genes, including the Sry gene, which plays a pivotal role in driving testes development.

In the study published in Science, the researchers investigated the role of the Wt1 gene in sex development. They created mice with genetic alterations in Wt1 to understand its effects. They found that one form of the WT1 protein (-KTS) is vital for gonad formation, as its absence prevented the formation of Sertoli and granulosa cells in both XY and XX mice.

In mice where Wt1 was mutated to only produce the -KTS form of the protein, the researchers observed that an excess of -KTS was produced. This excessive -KTS reduced the expression of Sry in XY gonads and increased genes associated with ovarian development. As a result, the production of SRY never reached the threshold needed to initiate testes development, leading to female gonad development in XY mice.

This discovery has far-reaching implications for understanding early gonadal development and how decisions made at this stage affect the fate of the gonad and the individual's overall sex. It could also provide insights into genetic disorders of sex development. Moreover, it may offer valuable information about how WT1 functions in kidney development and kidney cancer.