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Stabilization of beta-catenin in XY gonads causes male-to-female sex-reversal.

Publication ,  Journal Article
Maatouk, DM; DiNapoli, L; Alvers, A; Parker, KL; Taketo, MM; Capel, B
Published in: Hum Mol Genet
October 1, 2008

During mammalian sex determination, expression of the Y-linked gene Sry shifts the bipotential gonad toward a testicular fate by upregulating a feed-forward loop between FGF9 and SOX9 to establish SOX9 expression in somatic cells. We previously proposed that these signals are mutually antagonistic with counteracting signals in XX gonads and that a shift in the balance of these factors leads to either male or female development. Evidence in mice and humans suggests that the male pathway is opposed by the expression of two signals, WNT4 and R-SPONDIN-1 (RSPO1), that promote the ovarian fate and block testis development. Both of these ligands can activate the canonical Wnt signaling pathway. Duplication of the distal portion of chromosome 1p, which includes both WNT4 and RSPO1, overrides the male program and causes male-to-female sex reversal in XY patients. To determine whether activation of beta-catenin is sufficient to block the testis pathway, we have ectopically expressed a stabilized form of beta-catenin in the somatic cells of XY gonads. Our results show that activation of beta-catenin in otherwise normal XY mice effectively disrupts the male program and results in male-to-female sex-reversal. The identification of beta-catenin as a key pro-ovarian and anti-testis signaling molecule will further our understanding of the mechanisms controlling sex determination and the molecular mechanisms that lead to sex-reversal.

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Published In

Hum Mol Genet

DOI

EISSN

1460-2083

Publication Date

October 1, 2008

Volume

17

Issue

19

Start / End Page

2949 / 2955

Location

England

Related Subject Headings

  • beta Catenin
  • Wnt4 Protein
  • Wnt Proteins
  • Testis
  • Signal Transduction
  • Sex Differentiation
  • Phenotype
  • Ovary
  • Mice, Transgenic
  • Mice, Inbred C57BL
 

Citation

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Maatouk, D. M., DiNapoli, L., Alvers, A., Parker, K. L., Taketo, M. M., & Capel, B. (2008). Stabilization of beta-catenin in XY gonads causes male-to-female sex-reversal. Hum Mol Genet, 17(19), 2949–2955. https://doi.org/10.1093/hmg/ddn193
Maatouk, Danielle M., Leo DiNapoli, Ashley Alvers, Keith L. Parker, Makoto M. Taketo, and Blanche Capel. “Stabilization of beta-catenin in XY gonads causes male-to-female sex-reversal.Hum Mol Genet 17, no. 19 (October 1, 2008): 2949–55. https://doi.org/10.1093/hmg/ddn193.
Maatouk DM, DiNapoli L, Alvers A, Parker KL, Taketo MM, Capel B. Stabilization of beta-catenin in XY gonads causes male-to-female sex-reversal. Hum Mol Genet. 2008 Oct 1;17(19):2949–55.
Maatouk, Danielle M., et al. “Stabilization of beta-catenin in XY gonads causes male-to-female sex-reversal.Hum Mol Genet, vol. 17, no. 19, Oct. 2008, pp. 2949–55. Pubmed, doi:10.1093/hmg/ddn193.
Maatouk DM, DiNapoli L, Alvers A, Parker KL, Taketo MM, Capel B. Stabilization of beta-catenin in XY gonads causes male-to-female sex-reversal. Hum Mol Genet. 2008 Oct 1;17(19):2949–2955.
Journal cover image

Published In

Hum Mol Genet

DOI

EISSN

1460-2083

Publication Date

October 1, 2008

Volume

17

Issue

19

Start / End Page

2949 / 2955

Location

England

Related Subject Headings

  • beta Catenin
  • Wnt4 Protein
  • Wnt Proteins
  • Testis
  • Signal Transduction
  • Sex Differentiation
  • Phenotype
  • Ovary
  • Mice, Transgenic
  • Mice, Inbred C57BL