title: WNT4/beta-catenin pathway maintains female germ cell survival by inhibiting activin betaB in the mouse fetal ovary.
abstract: Female germ cells are essential for organogenesis of the ovary; without them, ovarian follicles do not form and functional and structural characteristics of the ovary are lost. We and others showed previously that when either Wnt4 or beta-catenin was inactivated in the fetal ovary, female germ cells underwent degeneration. In this study, we set out to understand whether these two factors belong to the same pathway and how they maintain female germ cell survival. We found that activation of beta-catenin in somatic cells in the Wnt4 knockout ovary restored germ cell numbers, placing beta-catenin downstream of WNT4. In the absence of Wnt4 or beta-catenin, female germ cells entered meiosis properly; however, they underwent apoptosis afterwards. Activin betaB (Inhbb), a subunit of activins, was upregulated in the Wnt4 and beta-catenin knockout ovaries, suggesting that Inhbb could be the cause for the loss of female germ cells, which are positive for activin receptors. Indeed, removal of Inhbb in the Wnt4 knockout ovaries prevented female germ cells from undergoing degeneration. We conclude that WNT4 maintains female germ cell survival by inhibiting Inhbb expression via beta-catenin in the somatic cells. Maintenance of female germ cells hinge upon a delicate balance between positive (WNT4 and beta-catenin) and negative (activin betaB) regulators derived from the somatic cells in the fetal ovary.
authors.affiliation: Department of Veterinary Biosciences, University of Illinois, Urbana-Champaign, Illinois, United States of America.
authors.forename: Chia-Feng
authors.initials: CF
authors.lastname: Liu
authors.forename: Keith
authors.initials: K
authors.lastname: Parker
authors.forename: Humphrey H-C
authors.initials: HH
authors.lastname: Yao
mesh_terms: D000818:Animals; D017209:Apoptosis; D002470:Cell Survival; D005260:Female; D005333:Fetus; D005854:Germ Cells / Q000166:cytology*; D028322:Inhibin-beta Subunits / Q000037:antagonists & inhibitors*; D008540:Meiosis; D051379:Mice; D010053:Ovary / Q000166:cytology* / Q000196:embryology; D051153:Wnt Proteins / Q000378:metabolism*; D060528:Wnt4 Protein; D051176:beta Catenin / Q000378:metabolism*
chemical_list: C498905:Inhbb protein, mouse; D051153:Wnt Proteins; D060528:Wnt4 Protein; C555582:Wnt4 protein, mouse; D051176:beta Catenin; D028322:Inhibin-beta Subunits
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