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#Wnt4

3 public questions tagged with this topic.

sex determination-ll

XX mammals lacking Wnt4 exhibit:

Wnt4 indispensably maintains ovarian identity in XX mammals; its absence causes masculinization. Knockout XX mice display perinatal partial sex reversal with testis-like coelomic vessel development, ectopic steroidogenic cells synthesizing testosterone, persistence of Wolffian duct remnants, reduction of Müllerian ducts due to reduced Fst, and transdifferentiation of granulosa precursors. Germ cell meiosis entry fails, follicles deplete resembling polycystic phenotype. Human WNT4 mutations associate with androgen excess and absence of Müllerian structures. Phenotype reflects derepression of Sox9/Fgf9 male program when Wnt4/β-catenin antagonism removed.

Ref: NCBI, Wnt4 knockout phenotype - masculinized XX gonads; Gilbert Chapter 6 Ovarian maintenance.

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sex determination-ll

Expression of Wnt4 gene primarily promotes:

Wnt4 is secreted glycoprotein of Wnt family functioning as pivotal ovary-determining signal. Expressed in bipotential gonad and upregulated specifically in XX somatic cells, Wnt4 activates canonical β-catenin cascade via Frizzled receptors, leading to stabilization of β-catenin and transcription of Dax1, Fst and Foxl2. This promotes granulosa fate, survival of germ cells entering meiosis, vascular patterning typical of ovary and maintenance of Müllerian ducts. Wnt4 knockout XX mice exhibit partial female-to-male reversal with Wolffian duct persistence, androgen synthesis, oocyte loss and ectopic testis cords, revealing requirement.

Ref: Gilbert, Developmental Biology, 12th ed., Chapter 6: Wnt4 in ovary determination and Müllerian duct maintenance.

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Fertilization in mammals-lll

Wnt4 signaling promotes:

Sex determination in mammalian gonad involves antagonism between testis-promoting and ovary-promoting signals. WNT4 secreted by XX bipotential gonad activates beta-catenin signaling via RSPO1-LGR5 axis stabilizing beta-catenin, upregulating FOXL2 and repressing SOX9 and FGF9 testis pathway, driving granulosa differentiation, Müllerian duct retention and oogenesis. Wnt4 null XX mice display partial masculinization with ectopic testosterone synthesis and coelomic vessel formation. Overexpression in XY can feminize gonads. Hence WNT4 is canonical ovary-determining factor opposing Sertoli fate. It does not promote testis, Leydig or Sertoli lineage but ensures female pathway dominance when SRY absent, maintaining ovarian differentiation and fertility.

Ref: Vainio et al., Nature 1999: Wnt4 required for ovary differentiation via beta-catenin and repression of testis Fgf9 signaling.

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