title: Wnt4/5a signalling coordinates cell adhesion and entry into meiosis during presumptive ovarian follicle development.
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.
authors.affiliation: Laboratory of Developmental Biology, Department of Medical Biochemistry and Molecular Biology, Oulu Centre for Cell-Matrix Research, Institute of Biomedicine, Biocenter Oulu, University of Oulu, PO Box 5000, FIN-90220 Oulu, Finland.
authors.forename: Florence
authors.initials: F
authors.lastname: Naillat
authors.forename: Renata
authors.initials: R
authors.lastname: Prunskaite-Hyyryläinen
authors.forename: Ilkka
authors.initials: I
authors.lastname: Pietilä
authors.forename: Raija
authors.initials: R
authors.lastname: Sormunen
authors.forename: Tiina
authors.initials: T
authors.lastname: Jokela
authors.forename: Jingdong
authors.initials: J
authors.lastname: Shan
authors.forename: Seppo J
authors.initials: SJ
authors.lastname: Vainio
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D002454:Cell Differentiation; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental; D008540:Meiosis; D051379:Mice; D018345:Mice, Knockout; D006080:Ovarian Follicle / Q000166:cytology / Q000196:embryology / Q000254:growth & development* / Q000378:metabolism*; D000072516:Retinoic Acid 4-Hydroxylase; D015398:Signal Transduction; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D000071818:Wnt-5a Protein; D060528:Wnt4 Protein
chemical_list: D051153:Wnt Proteins; D000071818:Wnt-5a Protein; D060528:Wnt4 Protein; C555582:Wnt4 protein, mouse; C438615:Wnt5a protein, mouse; D003577:Cytochrome P-450 Enzyme System; C000607081:Cyp26b1 protein, mouse; D000072516:Retinoic Acid 4-Hydroxylase