Wnt4/5a signalling coordinates cell adhesion and entry into meiosis during presumptive ovarian follicle development

Hum Mol Genet. 2010 Apr 15;19(8):1539-50. doi: 10.1093/hmg/ddq027. Epub 2010 Jan 27.

Abstract

Germ cells are the foundation of an individual, since they generate the gametes and provide the unique genome established through meiosis. The sex-specific fate of the germline in mammals is thought to be controlled by somatic signals, which are still poorly characterized. We demonstrate here that somatic Wnt signalling is crucial for the control of female germline development. Wnt-4 maintains germ cell cysts and early follicular gene expression and provides a female pattern of E-cadherin and beta-catenin expression within the germ cells. In addition, we find that Stra8 expression is downregulated and the Cyp26b1 gene is expressed ectopically in the partially masculinized Wnt-4-deficient ovary. Wnt-4 may control meiosis via these proteins since the Cyp26b1 enzyme is known to degrade retinoic acid (RA) and inhibit meiosis in the male embryo, and Stra8 induces meiosis in the female through RA. Reintroduction of a Wnt-4 signal to the partially masculinized embryonic ovary, in fact, rescues the female property to a certain degree, as seen by inhibition of Cyp26b1 and induction of Irx3 gene expression. Wnt-4 deficiency allows only 20% of the germ cells to initiate meiosis in the ovary, whereas meiosis is inhibited completely in the Wnt-4/Wnt-5a double mutant. These findings indicate a critical role for Wnt signalling in meiosis. Thus, the Wnt signals are important somatic cell signals that coordinate presumptive female follicle development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Adhesion
  • Cell Differentiation
  • Cytochrome P-450 Enzyme System / genetics
  • Cytochrome P-450 Enzyme System / metabolism
  • Female
  • Gene Expression Regulation, Developmental
  • Meiosis*
  • Mice
  • Mice, Knockout
  • Ovarian Follicle / cytology
  • Ovarian Follicle / embryology
  • Ovarian Follicle / growth & development*
  • Ovarian Follicle / metabolism*
  • Retinoic Acid 4-Hydroxylase
  • Signal Transduction*
  • Wnt Proteins / genetics
  • Wnt Proteins / metabolism*
  • Wnt-5a Protein
  • Wnt4 Protein

Substances

  • Wnt Proteins
  • Wnt-5a Protein
  • Wnt4 Protein
  • Wnt4 protein, mouse
  • Wnt5a protein, mouse
  • Cytochrome P-450 Enzyme System
  • Cyp26b1 protein, mouse
  • Retinoic Acid 4-Hydroxylase