Gadd45g is required for timely Sry expression independently of RSPO1 activity.

Area of Science:

• Mammalian genetics
• Developmental biology
• Reproductive biology

Background:

• Mammalian sex determination relies on opposing pro-testis (SRY-SOX9-FGF9) and pro-ovary (RSPO1-WNT4-FOXL2) pathways.
• Previous research indicated GADD45g is crucial for early Sry expression in XY gonads.

Purpose of the Study:

• To further investigate the relationship between GADD45g and Sry in mammalian sex determination.
• To explore the role of RSPO1 zygosity in gonadal sex reversal.

Main Methods:

• Utilized gain- and loss-of-function genetics in mouse models (B6.YPOS).
• Assessed Sry and Sox9 expression levels at specific developmental time points (11.5 and 12.5 dpc).
• Examined phenotypic outcomes of gonadal development in genetically modified embryos.

Main Results:

• Overexpression of GADD45g rescued sex reversal in XY gonads by elevating Sry levels.
• RSPO1 zygosity, but not Foxl2, significantly influenced the degree of sex reversal in XY gonads.
• Loss of both GADD45g and RSPO1 rescued sex reversal phenotypically, but Sox9, not Sry, levels were rescued by 12.5 dpc.

Conclusions:

• GADD45g is indispensable for the timely activation of Sry in XY gonads, independent of RSPO1-WNT signaling.
• The interplay between GADD45g and RSPO1 influences the balance of pro-testis and pro-ovary pathways during sex determination.