4.7 Article

β-Catenin is essential for Mullerian duct regression during male sexual differentiation

Journal

DEVELOPMENT
Volume 138, Issue 10, Pages 1967-1975

Publisher

COMPANY OF BIOLOGISTS LTD
DOI: 10.1242/dev.056143

Keywords

beta-Catenin; AMH; MIS; Mullerian duct regression; Wnt4; Mouse

Funding

  1. National Kidney Foundation
  2. American Society of Nephrology
  3. Harvard Stem Cell Institute
  4. M.D. Anderson Cancer Center
  5. Lalor Foundation
  6. National Institutes of Health (NIH) [HD30284]
  7. Ben F. Love Chair
  8. Kleberg Foundation
  9. NIH Cancer Center [CA16672]

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During male sexual differentiation, the transforming growth factor-beta (TGF-beta) signaling molecule anti-Mullerian hormone (AMH; also known as Mullerian inhibiting substance, MIS) is secreted by the fetal testes and induces regression of the Mullerian ducts, the primordia of the female reproductive tract organs. Currently, the molecular identity of downstream events regulated by the AMH signaling pathway remains unclear. We found that male-specific Wnt4 expression in mouse Mullerian duct mesenchyme depends upon AMH signaling, implicating the WNT pathway as a downstream mediator of Mullerian duct regression. Inactivation of beta-catenin, a mediator of the canonical WNT pathway, did not affect AMH signaling activation in the Mullerian duct mesenchyme, but did block Mullerian duct regression. These data suggest that beta-catenin mediates AMH signaling for Mullerian duct regression during male sexual differentiation.

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