Practice question

Ovarian fate in mammals depends on stabilization and nuclear accumulation of β-catenin, key effector of canonical Wnt signaling. In absence of Sry, R-spondin1 binds Lgr4/5 receptors and inhibits Znrf3/Rnf43 ubiquitination of Frizzled, amplifying Wnt4 signal. This inhibits Gsk3β-mediated destruction complex containing Axin and Apc, allowing β-catenin to accumulate and enter nucleus. Nuclear β-catenin partners with Lef1/Tcf to activate female genes Foxl2, Fst, Wnt4 and repress Sox9/Fgf9. This reciprocal inhibition ensures ovarian differentiation; deletion causes XX masculinization with ectopic Sox9 and testis vasculature.