Practice question

R-spondin1 encoded by Rspo1 is secreted potentiator of Wnt signaling indispensable for ovary determination. It binds Lgr receptors and simultaneously inhibits E3 ligases Znrf3/Rnf43, stabilizing Frizzled surface expression and sensitizing pre-granulosa cells to Wnt4 ligand. Enhanced signaling activates Disheveled, suppresses Gsk3β, causing β-catenin stabilization and nuclear translocation to drive female program. Human RSPO1 recessive mutations cause complete female-to-male sex reversal with XX testes, palmoplantar hyperkeratosis, while knockout mice show masculinized gonads lacking Wnt4 activation, demonstrating its role as organizer of ovarian pathway.