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#Disheveled protein

2 public questions tagged with this topic.

amphibian -ll

Disheveled protein (Dsh) during amphibian development is initially located at the:

In Xenopus unfertilized egg Dishevelled protein associated with vesicles anchors to vegetal cortex via interaction with VegT-localizing machinery and kinesin motors. Vegetal pole cortex also holds Vg1 and Wnt11 mRNAs. Upon sperm entry, parallel microtubule array assembles and transports Dishevelled vesicles dorsally toward future dorsal side, 30 degrees opposite sperm entry. At dorsal vegetal cortex Dishevelled inhibits Axin-GSK3 complex stabilizing beta-catenin. Animal pole cortex initially depleted of Dishevelled, explaining dorsal determinant transport from vegetal pole to dorsal equator necessary for Gray crescent and Nieuwkoop center establishment.

Ref: Gilbert, Developmental Biology, 12th ed., Chapter 8: Dishevelled localization at vegetal cortex and dorsal translocation.

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sex determination-ll

Which gene stimulates Disheveled protein to promote ovary development?

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.

Ref: Nature Reviews Genetics, 2017, Rspo1-Wnt4-β-catenin axis in mammalian ovary development.

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