Wednesday, November 8, 2023

Female sex determining gene identified in mice


Researchers from the Francis Crick Institute and the University Côte d'Azur, in collaboration with labs in France and Switzerland, made a breakthrough by identifying the key role of the Wt1 gene in early ovary development in mice. In mice, the presence of XY or XX chromosomes leads to testes or ovaries development. This outcome is determined by the activity of specific genes including the Sry gene on the Y chromosome (responsible for testes development). The research revealed that the -KTS form of the Wt1 protein is important for the formation of both Sertoli and granulosa cells in gonad development. When the researchers genetically manipulated mice to produce only the -KTS form of the protein, an excess of -KTS inhibited the expression of Sry in XY gonads (which prevents testes development). XY mice with an abundance of -KTS developed female gonads which demonstrated that -KTS is a key early trigger for female gonad development regardless of the chromosome configuration (XX or XY).

In humans mutations in WT1 can lead to Frasier syndrome, which affects kidney function and gonad development. Individuals with XY chromosomes and Frasier syndrome develop ovaries, which degenerate before birth. This discovery not only provides insight into the crucial early stages of gonad development and its impact on an individual's sex determination but also has broader implications for understanding WT1's role in kidney development. Wilms tumor, which is a type of kidney cancer, is also an uncovering mechanism underlying cell fate determination.

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